Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV001195278 | SCV001365587 | likely pathogenic | Rare genetic deafness | 2020-04-02 | criteria provided, single submitter | clinical testing | The p.Lys1003AsnfsX55 variant in MYO15A has not been previously reported in individuals with hearing loss and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1003 and leads to a premature termination codon 55 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the MYO15A gene is an established disease mechanism in autosomal recessive hearing loss. 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: PVS1, PM2. |
| Labcorp Genetics |
RCV003770193 | SCV004640819 | pathogenic | not provided | 2023-01-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys1003Asnfs*55) in the MYO15A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO15A are known to be pathogenic (PMID: 17546645). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYO15A-related conditions. ClinVar contains an entry for this variant (Variation ID: 929937). For these reasons, this variant has been classified as Pathogenic. |