Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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. |
Ce |
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, |
RCV000679827 | SCV000804818 | pathogenic | Deafness | 2018-09-10 | no assertion criteria provided | research | |
University of Washington Center for Mendelian Genomics, |
RCV001291098 | SCV001479464 | likely pathogenic | Hearing loss, autosomal recessive | no assertion criteria provided | research | ||
Natera, |
RCV001834957 | SCV002088459 | uncertain significance | Usher syndrome type 1B | 2021-06-19 | no assertion criteria provided | clinical testing |