Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000270527 | SCV000344558 | uncertain significance | not provided | 2016-09-08 | criteria provided, single submitter | clinical testing | |
| Molecular Diagnosis Center for Deafness | RCV002224965 | SCV001984935 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV000270527 | SCV003248763 | pathogenic | not provided | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2212 of the MYO15A protein (p.Glu2212Lys). This variant is present in population databases (rs371352836, gnomAD 0.006%). This missense change has been observed in individuals with autosomal recessive deafness (PMID: 26969326, 35346193; Invitae). ClinVar contains an entry for this variant (Variation ID: 290066). 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 MYO15A protein function. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330628 | SCV004038988 | uncertain significance | not specified | 2023-08-10 | criteria provided, single submitter | clinical testing | Variant summary: MYO15A c.6634G>A (p.Glu2212Lys) results in a conservative amino acid change located in the MyTH4 domain (IPR000857) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 249022 control chromosomes (gnomAD). c.6634G>A has been reported in the literature in individuals affected with Autosomal Recessive Nonsyndromic Hearing Loss (Sloan-Heggen_2016, Fu_2022, Wonkam_2022), and one patient was reported as compound heterozygous with a pathogenic variant. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26969326, 35346193, 35440622). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |