ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.9882C>G (p.Cys3294Trp) (rs749228276)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000593818 SCV000704988 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing
Invitae RCV000593818 SCV001206278 pathogenic not provided 2020-09-17 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tryptophan at codon 3294 of the USH2A protein (p.Cys3294Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is present in population databases (rs749228276, ExAC 0.003%). This variant has been observed in combination with another USH2A variant in individuals affected with retinitis pigmentosa and to segregate with disease in families (PMID: 24043777, 28130426, 28041643). ClinVar contains an entry for this variant (Variation ID: 438036). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075611 SCV001241238 pathogenic Retinal dystrophy 2019-01-31 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376250 SCV001573327 uncertain significance Retinitis pigmentosa 39 2021-04-08 criteria provided, single submitter research The USH2A c.9882C>G variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PP1. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Broad Institute Rare Disease Group, Broad Institute RCV000504661 SCV001950425 uncertain significance Retinitis pigmentosa 2021-04-01 criteria provided, single submitter curation The p.Cys3294Trp variant in USH2A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP1. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504661 SCV000598846 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research

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.