ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.1136G>A (p.Gly379Asp) (rs202174251)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041250 SCV000064941 uncertain significance not specified 2020-03-04 criteria provided, single submitter clinical testing The p.Gly379Asp variant in USH1C has been reported in one family with Usher syndrome; however, a second USH1C variant was not identified on the other allele (Aparisi 2010). It has also been identified by our laboratory in 1 proband with hearing loss who had an alternate genetic etiology identified. This variant is present in 0.02% (22/129188) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org), and it has been reported in ClinVar (Variation ID 47975). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3.
Invitae RCV001244821 SCV001418065 uncertain significance not provided 2019-12-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 379 of the USH1C protein (p.Gly379Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs202174251, ExAC 0.02%). This variant has been observed in individual(s) with Usher syndrome (PMID: 21203349). ClinVar contains an entry for this variant (Variation ID: 47975). 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 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.
Natera, Inc. RCV001273249 SCV001456079 uncertain significance Usher syndrome, type 1C 2020-09-16 no assertion criteria provided clinical testing

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