Comment on list classification: New gene added by Miranda Durkie. Based on the expert review this gene was added as an Amber gene.
Created: 5 Oct 2020, 2:11 p.m. | Last Modified: 5 Oct 2020, 2:11 p.m.
Panel Version: 2.6
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
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
Created: 30 Jul 2020, 11:54 a.m. | Last Modified: 20 Jan 2022, 9:15 a.m.
Panel Version: 2.10
Mode of inheritance
Tag Q1_22_NHS_review tag was added to gene: TRPV6.
Mode of inheritance for gene: TRPV6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Gene: trpv6 has been classified as Amber List (Moderate Evidence).
Publications for gene: TRPV6 were set to PMID: 31930989; 32383311
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