Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000036058 | SCV000059710 | likely benign | not specified | 2011-11-01 | criteria provided, single submitter | clinical testing | Ala536Thr in exon 14 of MYO7A: This variant is not expected to have clinical sig nificance because it has been identified by our laboratory in one individual who also carried two pathogenic MYO7A variants. In addition, computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein primarily based upon a lack of conservation across species including mam mals. Of note, opossum, chicken, frog and zebrafish have a threonine (Thr) at th is position despite high nearby amino acid conservation. |
Invitae | RCV001049904 | SCV001213978 | uncertain significance | not provided | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 536 of the MYO7A protein (p.Ala536Thr). This variant is present in population databases (rs201046979, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 43154). 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 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 |
RCV001049904 | SCV003805175 | uncertain significance | not provided | 2022-08-18 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |