Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Otolaryngology – Head & Neck Surgery, |
RCV001375262 | SCV001571740 | likely pathogenic | Hearing impairment | 2021-04-12 | criteria provided, single submitter | clinical testing | PS1_Strong, PM2_Moderate, PP3_Supporting |
Invitae | RCV003558389 | SCV004276913 | pathogenic | not provided | 2023-08-08 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 402262). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1414 of the MYO15A protein (p.Glu1414Lys). RNA analysis indicates that this missense change induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individuals with deafness (PMID: 21917145, 32747562). It has also been observed to segregate with disease in related individuals. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYO15A protein function. Studies have shown that this missense change results in skipping of exon 11, but is expected to preserve the integrity of the reading-frame (PMID: 32747562). For these reasons, this variant has been classified as Pathogenic. |
Hereditary Research Laboratory, |
RCV000454215 | SCV000538100 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | 2016-06-04 | no assertion criteria provided | research | Severe to Profound SNHL |