Amyloidosis

Gene: CST3

Amber List (moderate evidence)

CST3 (cystatin C)
EnsemblGeneIds (GRCh38): ENSG00000101439
EnsemblGeneIds (GRCh37): ENSG00000101439
OMIM: 604312, Gene2Phenotype
CST3 is in 3 panels

1 review

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Demoting from green to amber. Same substitution L68Q in all cases reported so far, with it appearing to be a founder mutation in the Icelandic cases, with only one sporadic case from a non-Icelandic individual. Agreement for the amber rating was confirmed with members of the GMS renal specialist test group.
Created: 12 Sep 2019, 3:48 p.m. | Last Modified: 8 Oct 2019, 1:07 p.m.
Panel Version: 0.18
Associated with Cerebral amyloid angiopathy (#105150) in PubMed

PMID: 2900981 - Palsdottir et al 1988 - abstract only accessed - 8 families with Hereditary cystatin C amyloid angiopathy and a mutation in the codon for leucine at position 68. The mutation affects a Alu I restriction site and from this it has been found that the mutation is transmitted only in affected members of the families.

PMID: 3495457 - Abrahamson et al 1987 - 1 case - report that the deposited fragment from a patient with hereditary cerebral hemorrhage with amyloidosis had a L68Q substitution.

PMID: 1352269 - Abrahamson et al 1992 - 4 HCCAA patients of four different families were analyzed by nucleotide sequencing; the HCCAA-causing mutation in all families was found to be a single T----A substitution in the codon for amino acid residue 68 of cystatin C.

PMID: 3673496 - Jensson et al 1987 - abstract only accessed - but OMIM report that they found abnormal cystatin C protein sequences in the amyloid protein deposited in patients with Icelandic-type amyloidosis. Abnormalities included absence of 10 amino acids from the amino terminal and an amino acid substitution at position 58, which corresponded to position 68 in cystatin C.

PMID: 7482672 - Graffagnino et al 1995 - report a case of sporadic Cerebral amyloid angiopathy (CAA) with intracerebral hemorrhage (ICH) in an elderly Croatian man with a mutation in cystatin C identical to that found in Icelandic hereditary cerebral hemorrhage with amyloidosis.

Same substitution L68Q in all cases reported so far, with it appearing to be a founder mutation in the Icelandic cases, with only one sporadic cases from a non-Icelandic individual.
Created: 13 Aug 2019, 3 p.m. | Last Modified: 13 Aug 2019, 3 p.m.
Panel Version: 0.7
This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group.Gene Symbol submitted: CST3;Suggested initial gene rating: Green;Evidence for inclusion: none provided;Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided. Other Comments: Already on the Periodic Fever Syndrome App, but evidence is red
Created: 2 Feb 2019, 3:49 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
105150

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • Cerebral amyloid angiopathy 105150
OMIM
604312
Clinvar variants
Variants in CST3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Sep 2019, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: CST3 were changed from 105150 to Cerebral amyloid angiopathy 105150

12 Sep 2019, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: CST3 were set to 2900981

12 Sep 2019, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: cst3 has been classified as Amber List (Moderate Evidence).

2 Feb 2019, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Eleanor Williams (Genomics England Curator)

gene: CST3 was added gene: CST3 was added to Amyloidosis. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: CST3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CST3 were set to 2900981 Phenotypes for gene: CST3 were set to 105150