ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.121G>A (p.Val41Met)

gnomAD frequency: 0.00003  dbSNP: rs780439529
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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 RCV001195265 SCV001365573 uncertain significance not specified 2019-07-09 criteria provided, single submitter clinical testing The p.Val41Met variant in USH1C has not been previously reported in individuals with hearing loss or Usher syndrome but has been identified in 0.005% (6/128842) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). 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.
GeneDx RCV001664744 SCV001873913 uncertain significance not provided 2021-08-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); 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 RCV001664744 SCV003519818 uncertain significance not provided 2022-07-19 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 41 of the USH1C protein (p.Val41Met). This variant is present in population databases (rs780439529, gnomAD 0.004%). 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: 929925). 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: "Tolerated"; PolyPhen-2: "Possibly 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.
Ambry Genetics RCV002560194 SCV003680289 uncertain significance Inborn genetic diseases 2021-09-16 criteria provided, single submitter clinical testing The c.121G>A (p.V41M) alteration is located in exon 3 (coding exon 3) of the USH1C gene. This alteration results from a G to A substitution at nucleotide position 121, causing the valine (V) at amino acid position 41 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001833757 SCV002087753 uncertain significance Usher syndrome type 1C 2020-02-13 no assertion criteria provided clinical testing

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