ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.13126T>G (p.Trp4376Gly)

dbSNP: rs775490668
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670549 SCV000795412 uncertain significance Usher syndrome type 2A; Retinitis pigmentosa 39 2017-11-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001295874 SCV001484825 uncertain significance not provided 2022-08-15 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 4376 of the USH2A protein (p.Trp4376Gly). This variant is present in population databases (rs775490668, gnomAD 0.02%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 32581362). ClinVar contains an entry for this variant (Variation ID: 438010). 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 RCV001778981 SCV002014913 uncertain significance not specified 2023-11-13 criteria provided, single submitter clinical testing Variant summary: USH2A c.13126T>G (p.Trp4376Gly) results in a non-conservative amino acid change located in the Fibronectin type III domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250730 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance.c.13126T>G has been reported in the literature in two individuals affected with retinitis pigmentosa (Carss_2017). This report does not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28041643, 32581362, 32176120). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab RCV003449424 SCV004181907 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001829436 SCV004181908 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000505006 SCV000598782 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
Natera, Inc. RCV001829436 SCV002088280 uncertain significance Usher syndrome type 2A 2020-04-20 no assertion criteria provided clinical testing

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