Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000217876 | SCV000270533 | likely benign | not specified | 2015-06-16 | criteria provided, single submitter | clinical testing | p.Tyr1244His in exon 30 of MYO3A: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, Egyptian jerboa, brush-tailed rat, and platypus have a histidine (His) at this position. It has been identified in (9/10140) of African chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs14 8993025). |
Illumina Laboratory Services, |
RCV001107711 | SCV001264887 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 30 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Invitae | RCV001853416 | SCV002225680 | uncertain significance | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1244 of the MYO3A protein (p.Tyr1244His). 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. 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 MYO3A protein function. ClinVar contains an entry for this variant (Variation ID: 227667). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. This variant is present in population databases (rs148993025, gnomAD 0.06%). |