ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.12560G>T (p.Arg4187Leu)

dbSNP: rs147304271
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000221966 SCV000272888 uncertain significance not specified 2015-03-02 criteria provided, single submitter clinical testing The p.Arg4187Leu variant in USH2A has not been previously reported in individual s with hearing loss. This variant has been identified in 1/11530 Latino chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs147304271. Although this variant has been seen in the general populatio n, its frequency is not high enough to rule out a pathogenic role. Computationa l prediction tools and conservation analyses do not provide strong support for o r against an impact to the protein. In summary, the clinical significance of the p.Arg4187Leu variant is uncertain.
Invitae RCV001857754 SCV002118285 uncertain significance not provided 2022-08-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 4187 of the USH2A protein (p.Arg4187Leu). This variant is present in population databases (rs147304271, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 229618). 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.
Genome-Nilou Lab RCV003454602 SCV004181983 uncertain significance Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001833218 SCV004181984 uncertain significance Usher syndrome type 2A 2023-11-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV001833218 SCV002088300 uncertain significance Usher syndrome type 2A 2019-11-11 no assertion criteria provided clinical testing

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