ClinVar Miner

Submissions for variant NM_000394.4(CRYAA):c.346C>T (p.Arg116Cys)

dbSNP: rs74315439
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000018469 SCV001209233 pathogenic Cataract 9 multiple types 2023-04-30 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg116 amino acid residue in CRYAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18302245, 20079887, 22045060, 22216983). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects CRYAA function (PMID: 10684623, 11123904, 18085469, 22045060, 22140512, 22347476). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CRYAA protein function. ClinVar contains an entry for this variant (Variation ID: 16957). This missense change has been observed in individual(s) with autosomal dominant congenital cataract (PMID: 9467006, 16735993, 17296897). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 116 of the CRYAA protein (p.Arg116Cys).
CeGaT Center for Human Genetics Tuebingen RCV001091467 SCV001247533 pathogenic not provided 2019-12-01 criteria provided, single submitter clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc RCV000018469 SCV005416049 pathogenic Cataract 9 multiple types criteria provided, single submitter clinical testing PM2_Supporting+PM5+PS3_Supporting+PS4_Moderate+PP1_Strong+PP4
OMIM RCV000018469 SCV000038751 pathogenic Cataract 9 multiple types 2007-02-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.