ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.2296T>C (p.Cys766Arg) (rs368687374)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001040831 SCV001204421 likely pathogenic not provided 2020-09-28 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 766 of the USH2A protein (p.Cys766Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is present in population databases (rs368687374, ExAC 0.01%). This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 23591405, 25404053, 30924848, Invitae). ClinVar contains an entry for this variant (Variation ID: 812458). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Blueprint Genetics RCV001073915 SCV001239480 pathogenic Retinal dystrophy 2018-06-18 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV001003278 SCV001950415 likely pathogenic Retinitis pigmentosa 2021-04-01 criteria provided, single submitter curation The p.Cys766Arg 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, PP3, PM3-S. Based on this evidence we have classified this variant as Likely Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
Sharon lab,Hadassah-Hebrew University Medical Center RCV001003278 SCV001161361 likely pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research

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