ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.13165T>C (p.Tyr4389His)

dbSNP: rs2102665721
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002003580 SCV002274273 uncertain significance not provided 2022-05-12 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 4389 of the USH2A protein (p.Tyr4389His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 32675063). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003331261 SCV004038375 uncertain significance not specified 2023-08-07 criteria provided, single submitter clinical testing Variant summary: USH2A c.13165T>C (p.Tyr4389His) results in a conservative amino acid change located in the Fibronectin type III (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250602 control chromosomes (gnomAD). c.13165T>C has been reported in the literature in individuals affected with nonsyndromic retinitis pigmentosa (Zhu_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 32675063). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Genome-Nilou Lab RCV003453923 SCV004181898 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003453922 SCV004181899 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
GeneDx RCV002003580 SCV005332564 uncertain significance not provided 2024-03-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32675063)

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