Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV002224976 | SCV005645966 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | 2024-01-06 | criteria provided, single submitter | clinical testing | |
| Laboratory of Human Genetics, |
RCV004719041 | SCV005324776 | pathogenic | Hearing loss, autosomal recessive | 2024-05-01 | criteria provided, single submitter | research | The MYO15A NM_016239.3:c.4252G>A variant has extremely low frequency in gnomAD population databases, For recessive disorders, detected in trans with a pathogenic variant, or in a homozygous or compound heterozygous state in affected cases (PM3), computational prediction tools unanimously support a deleterious effect on the gene (PP3). In this report it was found in trans with c.8080C>A, in two affected siblings born from unrelated couple. |
| Labcorp Genetics |
RCV001572126 | SCV002186122 | pathogenic | not provided | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1418 of the MYO15A protein (p.Gly1418Arg). This variant is present in population databases (rs753790346, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive deafness (PMID: 25373420, 30953472; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1120059). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| Molecular Diagnosis Center for Deafness | RCV002224976 | SCV001984899 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | criteria provided, single submitter | clinical testing | ||
| Gene |
RCV001572126 | SCV001796710 | pathogenic | not provided | 2023-12-08 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34416374, 25373420, 30953472, 35346193) |
| Laboratory for Molecular Medicine, |
RCV001449688 | SCV001652940 | likely pathogenic | Rare genetic deafness | 2023-06-19 | criteria provided, single submitter | clinical testing | The p.Gly1418Arg variant in MYO15A has been previously reported in three compound heterozygous individuals with congenital profound hearing loss (Park 2014 PMID: 25373420, Zhang 2019 PMID: 30953472, LMM internal data). This variant has been identified in 0.0065% (1/15280) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2); however, this frequency is low enough to be consistent with a recessive allele frequency. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PM3_Strong, PM2_Supporting, PP3. |