Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000155931 | SCV000205643 | uncertain significance | not specified | 2013-08-16 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The Cys635Arg v ariant in MYO7A has not been reported in individuals with hearing loss and is ab sent from large population studies. Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Cy s635Arg variant may impact the protein, particularly in light of the alteration of a Cysteine residue which is more likely to affect protein structure. In summa ry, the clinical significance of this variant cannot be determined with certaint y; however based upon the computational data and absence in the general populati on, we would lean towards a more likely pathogenic role. |
| Invitae | RCV001347350 | SCV001541606 | uncertain significance | not provided | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 635 of the MYO7A protein (p.Cys635Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Usher syndrome type 1 (PMID: 27743452). ClinVar contains an entry for this variant (Variation ID: 179146). 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. 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 |
RCV001347350 | SCV001819255 | likely pathogenic | not provided | 2019-12-10 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28944237, 27743452) |