ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.4505A>G (p.Asp1502Gly)

gnomAD frequency: 0.00001  dbSNP: rs757460257
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Total submissions: 6
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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 RCV000604476 SCV000731730 uncertain significance not specified 2017-07-11 criteria provided, single submitter clinical testing The p.Asp1502Gly variant in MYO7A has been previously reported in 1 individual w ith Usher syndrome; however, the individual was also reported to have 2 addition al truncating variants in MYO7A identified (Le Quesne Stabej 2012; https://grena da.lumc.nl/LOVD2/Usher_montpellier). This variant has been identified in 2/30782 South Asian chromosomes and in 1/18866 East Asian chromosomes by the Genome Agg regation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs757460257); however, its frequency is not high enough to rule out a pathogenic role. Comput ational prediction tools suggest the possible creation of a cryptic 5' splice si te; however, this information is not predictive enough to determine pathogenicit y. Additional computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predict ive enough to determine pathogenicity. In summary, the clinical significance of the p.Asp1502Gly variant is uncertain.
CeGaT Center for Human Genetics Tuebingen RCV001091734 SCV001247938 likely pathogenic not provided 2019-10-01 criteria provided, single submitter clinical testing
Invitae RCV001091734 SCV004551670 uncertain significance not provided 2023-01-09 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 517448). This missense change has been observed in individual(s) with deafness and/or Usher syndrome (PMID: 22135276, 30303587). This variant is present in population databases (rs757460257, gnomAD 0.006%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1502 of the MYO7A protein (p.Asp1502Gly).
Center for Statistical Genetics, Columbia University RCV000679827 SCV000804818 pathogenic Deafness 2018-09-10 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV001291098 SCV001479464 likely pathogenic Hearing loss, autosomal recessive no assertion criteria provided research
Natera, Inc. RCV001834957 SCV002088459 uncertain significance Usher syndrome type 1B 2021-06-19 no assertion criteria provided clinical testing

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