Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667248 | SCV000791669 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 | 2017-05-19 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002530709 | SCV003440570 | pathogenic | not provided | 2023-04-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.His133 amino acid residue in MYO7A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26969326; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 552051). This missense change has been observed in individual(s) with autosomal recessive Usher syndrome (PMID: 15823922, 16679490). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 133 of the MYO7A protein (p.His133Asp). |