Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000603496 | SCV000713270 | uncertain significance | not specified | 2017-05-31 | criteria provided, single submitter | clinical testing | The p.Val1362Met variant in MYO7A has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 1/111692 Europ ean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadi nstitute.org; dbSNP rs774773009). Although this variant has been seen in the gen eral population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical signif icance of the p.Val1362Met variant is uncertain. |
Invitae | RCV002529352 | SCV003283391 | uncertain significance | not provided | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 1362 of the MYO7A protein (p.Val1362Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs774773009, ExAC 0.002%). This variant has not been reported in the literature in individuals with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 505836). 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. |
Natera, |
RCV001829715 | SCV002088435 | uncertain significance | Usher syndrome type 1B | 2021-03-15 | no assertion criteria provided | clinical testing |