Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825260 | SCV000966550 | likely benign | not specified | 2018-10-31 | criteria provided, single submitter | clinical testing | The p.Met185Val variant in USH2A is classified as likely benign due to a lack of conservation across species. Several mammals including chimp, marmoset, squirre l monkey, alpaca, and Bactrian camel have a valine (Val) at this position. It ha s been identified in 1/30778 South Asian chromosomes by the Genome Aggregation D atabase (gnomAD, http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: B P4_Strong |
| Labcorp Genetics |
RCV001226960 | SCV001399292 | uncertain significance | not provided | 2024-09-05 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 185 of the USH2A protein (p.Met185Val). This variant is present in population databases (rs770266757, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 666775). 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 not expected to disrupt USH2A protein function with a negative 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. |
| Ambry Genetics | RCV002536042 | SCV003598766 | likely benign | Inborn genetic diseases | 2021-12-16 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |