ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.127G>A (p.Val43Met)

dbSNP: rs145500807
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Total submissions: 4
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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 RCV000041252 SCV000064943 uncertain significance not specified 2020-01-15 criteria provided, single submitter clinical testing The p.Val43Met variant in USH1C has been reported by our laboratory in 3 individuals with hearing loss; however, none of these individuals carried a second variant in USH1C and 2 individuals carried variants in other genes associated with hearing loss (LMM Data). This variant has been identified in 0.02% (19/113482) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org) and has been reported in ClinVar (Variation ID 47977). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting.
GeneDx RCV001570924 SCV001795297 uncertain significance not provided 2022-04-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001570924 SCV003253844 uncertain significance not provided 2022-10-28 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 43 of the USH1C protein (p.Val43Met). This variant is present in population databases (rs145500807, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with USH1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 47977). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. RCV001271302 SCV001452380 uncertain significance Usher syndrome type 1C 2020-04-11 no assertion criteria provided clinical testing

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