Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003734674 | SCV004539125 | pathogenic | not provided | 2023-06-05 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with deafness (PMID: 29692870). For these reasons, this variant has been classified as Pathogenic. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg2298*) 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). |
Laboratory for Molecular Medicine, |
RCV004018007 | SCV004848844 | pathogenic | Rare genetic deafness | 2022-11-03 | criteria provided, single submitter | clinical testing | The p.Arg2298X variant in MYO15A has been reported in at least 1 homozygous and 1 compound heterozygous individuals with nonsyndromic hearing loss and segregated with disease in 1 affected family member (Chen 2018 PMID: 29692870, Ma 2018 PMID: 30068307). It was identified in 1/68020 of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 2298, which is predicted to lead to a truncated or absent protein. Loss of function of the MYO15A gene is an established disease mechanism in autosomal recessive nonsyndromic hearing loss. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive nonsyndromic hearing loss. ACMG/AMP Criteria applied: PM2_Spporting, PVS1, PM3. |