ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.2240A>G (p.Gln747Arg)

gnomAD frequency: 0.00009  dbSNP: rs201600193
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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 RCV000155312 SCV000204998 uncertain significance not specified 2013-07-26 criteria provided, single submitter clinical testing The Gln747Arg variant in USH1C has not been identified in individuals with heari ng loss, but has been identified in 0.02% (1/4400) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS/; dbSNP rs201600193). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogeni c role. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. It should be noted that this variant occurs in exon 20 o f USH1C that is expressed in the ear and not the eye and therefore would likely only be relevant to nonsyndromic hearing loss, not Usher syndrome. In summary, a dditional data is needed to determine the clinical significance of this variant.
Counsyl RCV000668570 SCV000793195 uncertain significance Usher syndrome type 1C; Autosomal recessive nonsyndromic hearing loss 18A 2017-08-01 criteria provided, single submitter clinical testing
Invitae RCV002514993 SCV003511132 uncertain significance not provided 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 447 of the USH1C protein (p.Gln447Arg). This variant is present in population databases (rs201600193, 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: 178564). 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: "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. RCV001272252 SCV001454056 uncertain significance Usher syndrome type 1C 2020-09-16 no assertion criteria provided clinical testing

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