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Pancreatitis v3.2 Eleanor Williams Panel version 3.1 has been signed off on 2022-06-23
Pancreatitis v3.1 CELA3B Eleanor Williams Tag gene-checked tag was added to gene: CELA3B.
Pancreatitis v3.1 Ivone Leong Panel version 3.0 has been signed off on 2022-03-22
Pancreatitis v3.0 Ivone Leong promoted panel to version 3.0
Pancreatitis v2.12 CELA3B Ivone Leong Tag Q2_21_rating was removed from gene: CELA3B.
Tag Q2_21_NHS_review was removed from gene: CELA3B.
Pancreatitis v2.12 CELA3B Ivone Leong commented on gene: CELA3B: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Pancreatitis v2.11 CELA3B Ivone Leong Source Expert Review Green was added to CELA3B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Pancreatitis v2.10 TRPV6 Ivone Leong Tag Q1_22_NHS_review tag was added to gene: TRPV6.
Pancreatitis v2.10 TRPV6 Miranda Durkie changed review comment from: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature

Additional paper: PMID: 34923708 . Sequenced cohort of HCP and ICP and patients and identified 25 novel TRPV6 missense variants. Used functional Ca2+ assay to show 8 are functionally defective. Revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Therefore likely susceptibility allele as part of polygenic model. Keep at amber rating; to: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature

Additional paper: PMID: 34923708 added 20/01/2022. Sequenced cohort of HCP and ICP and patients and identified 25 novel TRPV6 missense variants. Used functional Ca2+ assay to show 8 are functionally defective. Revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Therefore likely susceptibility allele as part of polygenic model. Keep at amber rating 22/01/22
Pancreatitis v2.10 TRPV6 Miranda Durkie changed review comment from: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature; to: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature

Additional paper: PMID: 34923708 . Sequenced cohort of HCP and ICP and patients and identified 25 novel TRPV6 missense variants. Used functional Ca2+ assay to show 8 are functionally defective. Revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently coinherited with known risk variants in SPINK1, CTRC, and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Therefore likely susceptibility allele as part of polygenic model. Keep at amber rating
Pancreatitis v2.10 CELA3B Ivone Leong Classified gene: CELA3B as Amber List (moderate evidence)
Pancreatitis v2.10 CELA3B Ivone Leong Added comment: Comment on list classification: New gene added by Miranda Durkie. This gene is not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 31369399. Other affected members of this large family could not be tested and therefore the genetic status of the affected individuals are unknown. The family also has a variant in FOXN1, as the gene is not expressed in the pancreas the authors hypothesised that the FOXN1 variant was not causative.

PMID: 33565216. Four patients with p.Arg90Leu (c.269G>T) were from cases with familial chronic pancreatitis and young cases with idiopathic chronic pancreatitis (2 each). The familial chronic pancreatitis cases each have an affected first‐degree relative who have not been analysed yet.

This gene has been added as an Amber gene and will be reviewed by the GMS specialist group to see if there is enough evidence to promote to Green status.
Pancreatitis v2.10 CELA3B Ivone Leong Gene: cela3b has been classified as Amber List (Moderate Evidence).
Pancreatitis v2.9 CELA3B Ivone Leong Tag Q2_21_rating tag was added to gene: CELA3B.
Tag Q2_21_NHS_review tag was added to gene: CELA3B.
Pancreatitis v2.9 CELA3B Ivone Leong Phenotypes for gene: CELA3B were changed from Chronic Pancreatitis; Diabetes; Pancreatic cancer to Chronic Pancreatitis, MONDO:0005003; diabetes mellitus (disease), MONDO:0005015; Pancreatic cancer
Pancreatitis v2.8 CELA3B Ivone Leong Publications for gene: CELA3B were set to
Pancreatitis v2.7 CELA3B Miranda Durkie gene: CELA3B was added
gene: CELA3B was added to Pancreatitis. Sources: Literature
Mode of inheritance for gene: CELA3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CELA3B were set to Chronic Pancreatitis; Diabetes; Pancreatic cancer
Penetrance for gene: CELA3B were set to Incomplete
Mode of pathogenicity for gene: CELA3B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: CELA3B was set to GREEN
Added comment: PMID: 31369399 - 1 large family with 17 affected family members across 4 generations. Exome sequencing identified c.268C>T p.(Arg90Cys) in CELA3B gene in affected mother and affected daughter (not present in unaffected son). Does not segregate with disease in a further 6 unaffected family members. Functional studies showed both this variant and p.(Arg90Leu) variants cause translational upregulation of CELA3B, which, upon secretion and activation by
trypsin, leads to uncontrolled proteolysis and recurrent pancreatitis.
PMID: 33565216 - Sequenced CELA3B in 644 genetically unexplained French chronic pancreatitis (CP) patients (all unrelated) and 566 controls. No loss of function variants found, however found p.Arg90Leu (c.269G>T) in four patients but no controls.
Therefore 5 families identified with p.(Arg90Cys) or p.(Arg90Leu) and supporting functional assay for these variants only.
Sources: Literature
Pancreatitis v2.7 TRPV6 Ivone Leong Mode of inheritance for gene: TRPV6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Pancreatitis v2.6 TRPV6 Ivone Leong Classified gene: TRPV6 as Amber List (moderate evidence)
Pancreatitis v2.6 TRPV6 Ivone Leong Added comment: Comment on list classification: New gene added by Miranda Durkie. Based on the expert review this gene was added as an Amber gene.
Pancreatitis v2.6 TRPV6 Ivone Leong Gene: trpv6 has been classified as Amber List (Moderate Evidence).
Pancreatitis v2.5 TRPV6 Ivone Leong Publications for gene: TRPV6 were set to PMID: 31930989; 32383311
Pancreatitis v2.4 TRPV6 Miranda Durkie gene: TRPV6 was added
gene: TRPV6 was added to Pancreatitis. Sources: Literature
Mode of inheritance for gene: TRPV6 was set to Unknown
Publications for gene: TRPV6 were set to PMID: 31930989; 32383311
Phenotypes for gene: TRPV6 were set to Chronic pancreatitis
Penetrance for gene: TRPV6 were set to unknown
Review for gene: TRPV6 was set to AMBER
Added comment: PMID: 31930989: Heterozygous variants that affected function of the TRPV6 protein statistically over represented in cases vs controls (300 cases from Japan, 470 from France, 410 from Germany & >1000 controls). Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3–371.7; P ¼ 2.4 10–8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P ¼ 6.2 10–8). Homozygous mouse model given cerulein developed more severe pancreatitis than control mice (although homozygous / compound heterozygous disease in humans associated with transient neonatal hyperparathyroidism (OMIM 618188) with no reported pancreatitis). Also reported 20% had trans-heterozygous SPINK1 pathogenic variants.
PMID: 32383311: Chinese case control study of 669 cases and 609 controls showed over represented of confirmed loss of function alleles (9/669 [1.35%] vs. 1/609 [0.16%]; odds ratio = 8.29; p = .022).
Hypothesised treatment with Vitamin D may be beneficial.
Likely susceptibility allele therefore amber rating currently
Sources: Literature
Pancreatitis v2.4 PRSS2 Eleanor Williams Tag ensembl_ids_known_missing tag was added to gene: PRSS2.
Pancreatitis v2.4 PRSS2 Eleanor Williams commented on gene: PRSS2
Pancreatitis v2.3 Catherine Snow Panel version has been signed off
Pancreatitis v2.2 Catherine Snow Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Pancreatitis v2.0 Ivone Leong promoted panel to version 2.0
Pancreatitis v1.13 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off
Pancreatitis v1.12 CPA1 Ivone Leong commented on gene: CPA1: CPA1 will remain amber until further evidence can be provided before this will be promoted to green gene status.
Pancreatitis v1.12 CTRC Ivone Leong commented on gene: CTRC: CTRC will remain amber until further evidence can be provided before this will be promoted to green gene status.
Pancreatitis v1.12 Ivone Leong List of related panels changed from to R175
Pancreatitis v1.10 KRT8 Ivone Leong Classified gene: KRT8 as Amber List (moderate evidence)
Pancreatitis v1.10 KRT8 Ivone Leong Added comment: Comment on list classification: Promoted from red to amber based on expert review submitted by Miranda Durkie (Genetics).
Pancreatitis v1.10 KRT8 Ivone Leong Gene: krt8 has been classified as Amber List (Moderate Evidence).
Pancreatitis v1.9 KRT8 Ivone Leong Mode of inheritance for gene: KRT8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Pancreatitis v1.8 KRT8 Ivone Leong Added comment: Comment on publications: PMID: 29173301 refers to Xiao et al J Pediatr. 2017 Dec;191:158-163.
PMID: 27264265 refers to Sofia et al Mol Med. 2016 Sep;22:300-309.
Pancreatitis v1.8 KRT8 Ivone Leong Publications for gene: KRT8 were set to
Pancreatitis v1.7 KRT8 Miranda Durkie commented on gene: KRT8
Pancreatitis v1.7 CASR Ivone Leong Phenotypes for gene: CASR were changed from to Pancreatitis
Pancreatitis v1.6 CASR Ivone Leong Publications for gene: CASR were set to 29173301; 17853337; 26166472; 18680227; 20798521; 18938753
Pancreatitis v1.5 CPA1 Ivone Leong Mode of inheritance for gene: CPA1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pancreatitis v1.4 CPA1 Miranda Durkie reviewed gene: CPA1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 23955596, PMID: 28258133; Phenotypes: Chronic pancreatitis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pancreatitis v1.4 CFTR Ivone Leong Marked gene: CFTR as ready
Pancreatitis v1.4 CFTR Ivone Leong Added comment: Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.
Pancreatitis v1.4 CFTR Ivone Leong Gene: cftr has been classified as Green List (High Evidence).
Pancreatitis v1.4 PRSS1 Ivone Leong Marked gene: PRSS1 as ready
Pancreatitis v1.4 PRSS1 Ivone Leong Added comment: Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.
Pancreatitis v1.4 PRSS1 Ivone Leong Gene: prss1 has been classified as Green List (High Evidence).
Pancreatitis v1.4 SPINK1 Ivone Leong Marked gene: SPINK1 as ready
Pancreatitis v1.4 SPINK1 Ivone Leong Added comment: Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: SPINK1 is associated with the phenotype; however, penetrance is low. The Specialist Test Group agreed that there is enough evidence to rate this gene green.
Pancreatitis v1.4 SPINK1 Ivone Leong Gene: spink1 has been classified as Green List (High Evidence).
Pancreatitis v1.4 CASR Miranda Durkie reviewed gene: CASR: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 16497624, 26166472; Phenotypes: Pancreatitis; Mode of inheritance: Other
Pancreatitis v1.4 KRT8 Ivone Leong reviewed gene: KRT8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v1.4 CASR Ivone Leong reviewed gene: CASR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v1.4 PRSS2 Ivone Leong reviewed gene: PRSS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v1.4 CTSB Ivone Leong reviewed gene: CTSB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v1.4 CPA1 Ivone Leong reviewed gene: CPA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v1.4 CTRC Ivone Leong reviewed gene: CTRC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v1.4 CFTR Ivone Leong reviewed gene: CFTR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v1.4 SPINK1 Ivone Leong reviewed gene: SPINK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v1.4 PRSS1 Ivone Leong reviewed gene: PRSS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v1.3 KRT8 Ivone Leong gene: KRT8 was added
gene: KRT8 was added to Pancreatitis. Sources: NHS GMS
Mode of inheritance for gene: KRT8 was set to
Pancreatitis v1.3 CASR Ivone Leong Source NHS GMS was added to CASR.
Pancreatitis v1.3 PRSS2 Ivone Leong Source NHS GMS was added to PRSS2.
Pancreatitis v1.3 CTSB Ivone Leong Source NHS GMS was added to CTSB.
Pancreatitis v1.3 CPA1 Ivone Leong Source NHS GMS was added to CPA1.
Pancreatitis v1.3 CTRC Ivone Leong Source NHS GMS was added to CTRC.
Pancreatitis v1.3 CFTR Ivone Leong Source NHS GMS was added to CFTR.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pancreatitis v1.3 SPINK1 Ivone Leong Source NHS GMS was added to SPINK1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pancreatitis v1.3 PRSS1 Ivone Leong Source NHS GMS was added to PRSS1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pancreatitis v1.0 Ellen McDonagh promoted panel to version 1.0
Pancreatitis v0.48 PRSS1 Ellen McDonagh Added comment: Comment on mode of pathogenicity: Seems to be a gain-of-function mechanism.
Pancreatitis v0.48 PRSS1 Ellen McDonagh Mode of pathogenicity for gene: PRSS1 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Pancreatitis v0.47 CPA1 Louise Daugherty Phenotypes for gene: CPA1 were changed from chronic pancreatitis; hereditary chronic pancreatitis to Chronic pancreatitis; Hereditary chronic pancreatitis
Pancreatitis v0.46 CFTR Ellen McDonagh Phenotypes for gene: CFTR were changed from {Pancreatitis, hereditary} 167800 to {Pancreatitis, hereditary} 167800; Cystic fibrosis 219700
Pancreatitis v0.45 CFTR Ellen McDonagh Classified gene: CFTR as Green List (high evidence)
Pancreatitis v0.45 CFTR Ellen McDonagh Added comment: Comment on list classification: This gene has been promoted from Amber to Green, for the biallelic mode of inheritance, due to comments from Dr Ellen Thomas that exocrine pancreas dysfunction is an indication for diagnostic Cystic Fibrosis testing, and therefore this panel should cover the CFTR gene.
Pancreatitis v0.45 CFTR Ellen McDonagh Gene: cftr has been classified as Green List (High Evidence).
Pancreatitis v0.44 CFTR Ellen McDonagh Added comment: Comment on mode of inheritance: Changed to the biallelic form.
Pancreatitis v0.44 CFTR Ellen McDonagh Mode of inheritance for gene: CFTR was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Pancreatitis v0.43 CFTR Ellen Thomas reviewed gene: CFTR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cystic fibrosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Pancreatitis v0.43 MORC4 Ellen McDonagh edited their review of gene: MORC4: Changed rating: RED
Pancreatitis v0.43 SPINK1 Ellen McDonagh commented on gene: SPINK1
Pancreatitis v0.43 PRSS1 Ellen McDonagh commented on gene: PRSS1
Pancreatitis v0.43 MORC4 Ellen McDonagh commented on gene: MORC4
Pancreatitis v0.43 MORC4 Ellen McDonagh gene: MORC4 was added
gene: MORC4 was added to Pancreatitis. Sources: Literature
Mode of inheritance for gene: MORC4 was set to Unknown
Publications for gene: MORC4 were set to 29884332; 29173301; 28754779; 26820620; 26784911; 26002935; 25253127; 23143602; 28754779; 24002981
Pancreatitis v0.42 CLDN2 Ellen McDonagh edited their review of gene: CLDN2: Changed rating: RED
Pancreatitis v0.42 CXCL8 Ellen McDonagh edited their review of gene: CXCL8: Added comment: In a publicaton search, could not find evidence for variants in this gene to be causative of pancreatitis.; Changed rating: RED
Pancreatitis v0.42 PRSS2 Ellen McDonagh Deleted their comment
Pancreatitis v0.42 CTSB Ellen McDonagh Added comment: Comment on publications: Polymorphisms in this gene have been associated with pancreatitis or tropical calcific pancreatitis, and the cathepsin B gene is involved in the pathology of pancreatitis (see publications). There does not seem to be enough evidence at this time for rare loss of function variants in this gene to be causative of hereditary pancreatitis.
Pancreatitis v0.42 CTSB Ellen McDonagh Publications for gene: CTSB were set to 30455353; 30134826; 29229780; 29079517; 27226576; 22580415; 19900452; 16492714; 10995788
Pancreatitis v0.42 CTSB Ellen McDonagh edited their review of gene: CTSB: Changed rating: RED
Pancreatitis v0.42 CTSB Ellen McDonagh Added comment: Comment on publications: Polymorphisms in this gene have been associated with pancreatitis or tropical calcific pancreatitis, and the cathepsin B gene is involved in the pathology of pancreatitis (see publications). There does not seem to be enough evidence at this time for rare loss of function variants in this gene to be causative of hereditary pancreatitis.
Pancreatitis v0.42 CTSB Ellen McDonagh Publications for gene: CTSB were set to 30455353
Pancreatitis v0.41 CTSB Ellen McDonagh Added comment: Comment on publications: PMID: 30455353 - CTSC-deletion in mild and severe pancreatitis in vivo models was found to reduce the severity of pancreatitis compared to control mice.
Pancreatitis v0.41 CTSB Ellen McDonagh Publications for gene: CTSB were set to
Pancreatitis v0.40 CLDN2 Ellen McDonagh Publications for gene: CLDN2 were set to 29884332; 29173301; 28754779; 26820620; 26784911; 26002935; 25253127; 23143602; 28754779
Pancreatitis v0.39 CLDN2 Ellen McDonagh Publications for gene: CLDN2 were set to 29884332; 29173301; 28754779; 26820620; 26784911; 26002935; 25253127; 23143602
Pancreatitis v0.38 CLDN2 Ellen McDonagh Added comment: Comment on publications: Common polymorphisms at the CLDN2-MORC4 loci have been associated with chronic pancreatitis in numerous studies (see publications listed).
Pancreatitis v0.38 CLDN2 Ellen McDonagh Publications for gene: CLDN2 were set to
Pancreatitis v0.37 CEL Ellen McDonagh edited their review of gene: CEL: Changed rating: RED
Pancreatitis v0.37 CEL Ellen McDonagh Publications for gene: CEL were set to 29233499
Pancreatitis v0.36 CEL Ellen McDonagh Added comment: Comment on publications: PMID: 29233499 - suggests CEL is an interesting candidate gene links to pancreatic disease; a recombined allele between CEL and its pseudogene CELP has been discovered which encodes a chimeric protein with impaired secretion increasing the risk for chronic pancreatitis five-fold.
Pancreatitis v0.36 CEL Ellen McDonagh Publications for gene: CEL were set to
Pancreatitis v0.35 CCL2 Ellen McDonagh edited their review of gene: CCL2: Changed rating: RED
Pancreatitis v0.35 CCL2 Ellen McDonagh Added comment: Comment on publications: PMID: 23449669 - CCL2 knockout exacerbates chronic pancreatitis.
Pancreatitis v0.35 CCL2 Ellen McDonagh Publications for gene: CCL2 were set to
Pancreatitis v0.34 PRSS2 Ellen McDonagh commented on gene: PRSS2: Could not find evidence for an association with inherited pancreatitis.
Pancreatitis v0.34 PRSS2 Ellen McDonagh edited their review of gene: PRSS2: Changed rating: RED
Pancreatitis v0.34 CTRC Ellen McDonagh Classified gene: CTRC as Amber List (moderate evidence)
Pancreatitis v0.34 CTRC Ellen McDonagh Added comment: Comment on list classification: Demoting this gene from Green to Amber as it seems to be a susceptibility gene, rather than an isolated cause of inherited pancreatitis.
Pancreatitis v0.34 CTRC Ellen McDonagh Gene: ctrc has been classified as Amber List (Moderate Evidence).
Pancreatitis v0.31 PRSS2 Ellen McDonagh Added comment: Comment on publications: PMID: 16699518 - the G191R variant in this gene is deemed protective against chronic pancreatitis.
Pancreatitis v0.31 PRSS2 Ellen McDonagh Publications for gene: PRSS2 were set to 25253127; 23143602; 27846138; 26784911; 26002935; 26110235; 29884332; 19052022; 15776435; 16699518; 14695529
Pancreatitis v0.30 PRSS2 Ellen McDonagh Phenotypes for gene: PRSS2 were changed from to {Pancreatitis, chronic, protection against} 167800
Pancreatitis v0.29 PRSS2 Ellen McDonagh Added comment: Comment on publications: PMID: 14695529 - a mutation in PRSS1 causes increased transactivation of PRSS2.
Pancreatitis v0.29 PRSS2 Ellen McDonagh Publications for gene: PRSS2 were set to 25253127; 23143602; 27846138; 26784911; 26002935; 26110235; 29884332; 19052022; 15776435; 16699518; 18362849; 14695529
Pancreatitis v0.29 PRSS2 Ellen McDonagh Added comment: Comment on publications: PMID: 14695529 - a mutation in PRSS1 causes increased transactivation of PRSS2.
Pancreatitis v0.29 PRSS2 Ellen McDonagh Publications for gene: PRSS2 were set to 25253127; 23143602; 27846138; 26784911; 26002935; 26110235; 29884332; 19052022; 15776435; 16699518
Pancreatitis v0.28 PRSS2 Ellen McDonagh Added comment: Comment on publications: Multiple association studies for PRSS1-PRSS2 locus and chronic pancreatitis, tropical calfific pancreatitis, acute pancreatitis, alcoholic and non-alcoholic pancreatitis, sporadic pancreatitis.
Pancreatitis v0.28 PRSS2 Ellen McDonagh Publications for gene: PRSS2 were set to
Pancreatitis v0.27 CXCL8 Ellen McDonagh commented on gene: CXCL8
Pancreatitis v0.27 CTSB Ellen McDonagh commented on gene: CTSB
Pancreatitis v0.27 CASR Ellen McDonagh commented on gene: CASR: Variants in this gene seem to be a possible risk factor, unclear currently whether variants in this gene in isolation are causative of pancreatitis.
Pancreatitis v0.27 CASR Ellen McDonagh Added comment: Comment on publications: PMID: 26166472 - Overrepresentation of Rare CASR Coding Variants in a Sample of Young French Patients With Idiopathic Chronic Pancreatitis. PMID: 18680227 - case-control study in 57 patients and 21 controls found the R990G polymorphism was significantly associated with chronic pancreatitis (OR, 2.01; 95% CI, 1.12-3.59; P = 0.015).
Pancreatitis v0.27 CASR Ellen McDonagh Publications for gene: CASR were set to 29173301; 17853337
Pancreatitis v0.26 CASR Ellen McDonagh Added comment: Comment on publications: PMID: 29173301 - 5 children with variants in this gene with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP) were identified in next-generation sequencing of 10 genes, but unclear from the abstract whether these were considered diagnostic.
PMID: 17853337 - CASR gene was examined in patients with pancreatitis in primary hyperparathyroidism and no assoication with variants in this gene was found.
Pancreatitis v0.26 CASR Ellen McDonagh Publications for gene: CASR were set to
Pancreatitis v0.25 CTRB1 Ellen McDonagh edited their review of gene: CTRB1: Changed rating: RED
Pancreatitis v0.25 CTRB1 Ellen McDonagh Added comment: Comment on publications: PMID: 30076839 - an induced pancreatitis in vivo model revealed that CTRB1-deficient mice given cerulein had significant increases in intrapancreatic trypsin activity and developed more severe pancreatitis compared with control mice. The authors suggest that CTRB1 protects against secretagogue-induced pancreatitis by reducing trypsin activity.
Pancreatitis v0.25 CTRB1 Ellen McDonagh Publications for gene: CTRB1 were set to 28754779; 28951524
Pancreatitis v0.24 CTRB1 Ellen McDonagh Publications for gene: CTRB1 were set to
Pancreatitis v0.23 CTRB1 Ellen McDonagh commented on gene: CTRB1: PMID: 28754779 - identified CTRB1-CTRB2 as a new risk locus for alcoholic chronic pancreatitis and non-alcoholic chronic pancreatitis. A 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956, reported to changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk. PMID: 28951524 found no association in the Chinese population. Not enough evidence at this time for this to be a cause of monogenic pancreatitis.
Pancreatitis v0.23 CTRB2 Ellen McDonagh Phenotypes for gene: CTRB2 were changed from to risk factor for alcoholic and non-alcoholic chronic pancreatitis
Pancreatitis v0.22 CTRB2 Ellen McDonagh Publications for gene: CTRB2 were set to
Pancreatitis v0.21 CTRB2 Ellen McDonagh reviewed gene: CTRB2: Rating: RED; Mode of pathogenicity: None; Publications: 28754779, 28951524; Phenotypes: risk factor for alcoholic/non-alcoholic chronic pancreatitis; Mode of inheritance: None
Pancreatitis v0.21 CTRB1 Ellen McDonagh commented on gene: CTRB1
Pancreatitis v0.21 CLDN2 Ellen McDonagh commented on gene: CLDN2
Pancreatitis v0.21 CEL Ellen McDonagh commented on gene: CEL
Pancreatitis v0.21 CCL2 Ellen McDonagh commented on gene: CCL2
Pancreatitis v0.21 CASR Ellen McDonagh reviewed gene: CASR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Pancreatitis v0.21 Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease
Pancreatitis v0.20 CFTR Eleanor Williams Classified gene: CFTR as Amber List (moderate evidence)
Pancreatitis v0.20 CFTR Eleanor Williams Added comment: Comment on list classification: Rating Amber based on feedback from Genomics England clinical team.
Pancreatitis v0.20 CFTR Eleanor Williams Gene: cftr has been classified as Amber List (Moderate Evidence).
Pancreatitis v0.19 CPA1 Eleanor Williams Tag watchlist tag was added to gene: CPA1.
Pancreatitis v0.19 CPA1 Eleanor Williams Classified gene: CPA1 as Amber List (moderate evidence)
Pancreatitis v0.19 CPA1 Eleanor Williams Added comment: Comment on list classification: Rating Amber on advice from Genomics England clinical team.
Pancreatitis v0.19 CPA1 Eleanor Williams Gene: cpa1 has been classified as Amber List (Moderate Evidence).
Pancreatitis v0.18 CFTR Eleanor Williams Phenotypes for gene: CFTR were changed from to {Pancreatitis, hereditary} 167800
Pancreatitis v0.17 CFTR Eleanor Williams Publications for gene: CFTR were set to
Pancreatitis v0.16 CFTR Eleanor Williams Mode of inheritance for gene: CFTR was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pancreatitis v0.15 CFTR Eleanor Williams edited their review of gene: CFTR: Changed publications: 9725921, 15987793, 16134171, 16193325, 11729110, 23951356, 22427236, 25033378, 22658665, 26856995, 27555793, 1345141, 15749233, 25033378, 20977904, 22427236; Changed phenotypes: {Pancreatitis, hereditary} 167800; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pancreatitis v0.15 CFTR Eleanor Williams commented on gene: CFTR: Checking with Genomics England Clinical team as to the correct rating for this gene.
Pancreatitis v0.15 CFTR Eleanor Williams commented on gene: CFTR
Pancreatitis v0.15 CPA1 Eleanor Williams commented on gene: CPA1: Waiting on advice from Genomics England clinical team about the appropriate rating for this gene.
Pancreatitis v0.15 CPA1 Eleanor Williams Phenotypes for gene: CPA1 were changed from to chronic pancreatitis; hereditary chronic pancreatitis
Pancreatitis v0.14 CPA1 Eleanor Williams Added comment: Comment on publications: 28650851 is a review
Pancreatitis v0.14 CPA1 Eleanor Williams Publications for gene: CPA1 were set to
Pancreatitis v0.13 CPA1 Eleanor Williams commented on gene: CPA1
Pancreatitis v0.13 CTRC Eleanor Williams Phenotypes for gene: CTRC were changed from to {Pancreatitis, chronic, susceptibility to} 167800
Pancreatitis v0.12 CTRC Eleanor Williams Publications for gene: CTRC were set to
Pancreatitis v0.11 CTRC Eleanor Williams Added comment: Comment on mode of inheritance: From OMIM
Pancreatitis v0.11 CTRC Eleanor Williams Mode of inheritance for gene: CTRC was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pancreatitis v0.10 CTRC Eleanor Williams Classified gene: CTRC as Green List (high evidence)
Pancreatitis v0.10 CTRC Eleanor Williams Added comment: Comment on list classification: More than 3 cases of plausible disease causing variants found in association with this disorder.
Pancreatitis v0.10 CTRC Eleanor Williams Gene: ctrc has been classified as Green List (High Evidence).
Pancreatitis v0.9 CTRC Eleanor Williams commented on gene: CTRC
Pancreatitis v0.9 PRSS1 Eleanor Williams Tag cnv tag was added to gene: PRSS1.
Pancreatitis v0.9 PRSS1 Eleanor Williams Phenotypes for gene: PRSS1 were changed from to Pancreatitis, hereditary 167800
Pancreatitis v0.8 PRSS1 Eleanor Williams Added comment: Comment on publications: Publications from OMIM
Pancreatitis v0.8 PRSS1 Eleanor Williams Publications for gene: PRSS1 were set to
Pancreatitis v0.7 PRSS1 Eleanor Williams Mode of inheritance for gene: PRSS1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pancreatitis v0.6 PRSS1 Eleanor Williams Classified gene: PRSS1 as Green List (high evidence)
Pancreatitis v0.6 PRSS1 Eleanor Williams Added comment: Comment on list classification: More than 3 unrelated cases of plausible disease causing variants associated with the disorder.
Pancreatitis v0.6 PRSS1 Eleanor Williams Gene: prss1 has been classified as Green List (High Evidence).
Pancreatitis v0.5 PRSS1 Eleanor Williams reviewed gene: PRSS1: Rating: ; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pancreatitis v0.5 SPINK1 Eleanor Williams Phenotypes for gene: SPINK1 were changed from to Pancreatitis, hereditary 167800
Pancreatitis v0.4 SPINK1 Eleanor Williams Publications for gene: SPINK1 were set to
Pancreatitis v0.3 SPINK1 Eleanor Williams Added comment: Comment on mode of inheritance: OMIM has Pancreatitis, hereditary as AD inheritance and this appears to be correct for several variants reported.
Pancreatitis v0.3 SPINK1 Eleanor Williams Mode of inheritance for gene: SPINK1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pancreatitis v0.2 SPINK1 Eleanor Williams Classified gene: SPINK1 as Green List (high evidence)
Pancreatitis v0.2 SPINK1 Eleanor Williams Added comment: Comment on list classification: Three cases/families found with different plausible disease causing variants found.
Pancreatitis v0.2 SPINK1 Eleanor Williams Gene: spink1 has been classified as Green List (High Evidence).
Pancreatitis v0.1 SPINK1 Eleanor Williams commented on gene: SPINK1
Pancreatitis CPA1 Ioannis Sarantitis reviewed gene: CPA1
Pancreatitis CTRC Ioannis Sarantitis reviewed gene: CTRC
Pancreatitis CFTR Ioannis Sarantitis reviewed gene: CFTR
Pancreatitis SPINK1 Ioannis Sarantitis reviewed gene: SPINK1
Pancreatitis PRSS1 Ioannis Sarantitis reviewed gene: PRSS1
Pancreatitis CXCL8 Ellen McDonagh Added gene to panel
Pancreatitis CEL Ellen McDonagh Added gene to panel
Pancreatitis CCL2 Ellen McDonagh Added gene to panel
Pancreatitis CPA1 Ellen McDonagh Added gene to panel
Pancreatitis CLDN2 Ellen McDonagh Added gene to panel
Pancreatitis CTSB Ellen McDonagh Added gene to panel
Pancreatitis CASR Ellen McDonagh Added gene to panel
Pancreatitis CTRB2 Ellen McDonagh Added gene to panel
Pancreatitis CTRB1 Ellen McDonagh Added gene to panel
Pancreatitis CTRC Ellen McDonagh Added gene to panel
Pancreatitis SPINK1 Ellen McDonagh Added gene to panel
Pancreatitis CFTR Ellen McDonagh Added gene to panel
Pancreatitis PRSS2 Ellen McDonagh Added gene to panel
Pancreatitis PRSS1 Ellen McDonagh Added gene to panel