ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1901G>A (p.Arg634Gln)

gnomAD frequency: 0.00004  dbSNP: rs781812509
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000988604 SCV001138383 uncertain significance Autosomal recessive nonsyndromic hearing loss 2 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000994686 SCV001148373 uncertain significance not provided 2020-03-01 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001195389 SCV001365738 uncertain significance not specified 2019-11-06 criteria provided, single submitter clinical testing The p.Arg634Gln variant in MYO7A has been previously reported in an individual with moderate hearing loss who had a truncating MYO7A variant confirmed in trans (He 2018). This variant has been identified in 0.01% (1/8036) in African chromosomes by gnomAD (http://gnomad.broadinstitute.org). 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: PM3, PM2_Supporting, PP3.
GeneDx RCV000994686 SCV001988393 uncertain significance not provided 2022-05-04 criteria provided, single submitter clinical testing Observed with multiple variants in the MYO7A gene in a patient with hearing loss in published literature (He et al., 2018); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29178603)
Labcorp Genetics (formerly Invitae), Labcorp RCV000994686 SCV003455423 uncertain significance not provided 2024-07-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 634 of the MYO7A protein (p.Arg634Gln). This variant is present in population databases (rs781812509, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 802706). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO7A protein function with a positive predictive value of 95%. 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. RCV001827130 SCV002086590 uncertain significance Usher syndrome type 1B 2021-05-07 no assertion criteria provided clinical testing

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