ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.407G>A (p.Arg136Gln)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001241479 SCV001414501 uncertain significance not provided 2019-11-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 136 of the USH1C protein (p.Arg136Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs558663132, ExAC 0.05%). This variant has not been reported in the literature in individuals with USH1C-related conditions. 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV001449780 SCV001653056 uncertain significance not specified 2020-06-04 criteria provided, single submitter clinical testing The p.Arg136Gln variant in USH1C has been previously reported in 1 proband with Usher syndrome; however, a second variant in USH1C was not detected (PMID: 29625443). It has also been identified in 0.06% (19/30614) of South Asian Computational prediction tools and conservation analyses 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.

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