ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.634C>T (p.Arg212Cys)

gnomAD frequency: 0.00002  dbSNP: rs121965080
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001047241 SCV001211181 pathogenic not provided 2025-01-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 212 of the MYO7A protein (p.Arg212Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Usher syndrome (PMID: 15043528, 27957503). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 11851). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYO7A protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects MYO7A function (PMID: 18700726). This variant disrupts the p.Arg212 amino acid residue in MYO7A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7870171, 15043528, 24199935). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001047241 SCV005626465 pathogenic not provided 2024-07-11 criteria provided, single submitter clinical testing Published functional studies demonstrate this variant leads to loss of function of actin-activated ATPase activity (PMID: 18700726); A different missense change at this residue (p.(R212H)) has been reported as pathogenic in the published literature in association with Usher syndrome (PMID: 8900236, 15043528, 21873662); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 8900236, 36597107, 27957503, 18700726, 7870171, 15043528, 21873662)
Fulgent Genetics, Fulgent Genetics RCV005007838 SCV005632194 likely pathogenic Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2024-04-30 criteria provided, single submitter clinical testing
OMIM RCV000012625 SCV000032860 pathogenic Usher syndrome type 1B 1995-10-10 no assertion criteria provided literature only
Natera, Inc. RCV000012625 SCV001461547 pathogenic Usher syndrome type 1B 2020-09-16 no assertion criteria provided clinical testing

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