Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001729610 | SCV003474715 | uncertain significance | not provided | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2194 of the MYO15A protein (p.Arg2194Trp). This variant is present in population databases (rs773551819, gnomAD 0.03%). This missense change has been observed in individual(s) with deafness (PMID: 29907799; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 417946). 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 not expected to disrupt MYO15A protein function. 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. |
Gene |
RCV001729610 | SCV003933430 | likely pathogenic | not provided | 2023-06-12 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29907799) |
Division of Human Genetics, |
RCV000477772 | SCV000536903 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 3 | 2016-06-29 | no assertion criteria provided | research | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001729610 | SCV001980251 | uncertain significance | not provided | no assertion criteria provided | clinical testing |