Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000779208 | SCV000915749 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 3 | 2017-06-26 | criteria provided, single submitter | clinical testing | The MYO15A c.5492delG (p.Gly1831AspfsTer18) variant results in a frameshift and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is reported at a frequency of 0.000067 in the European (non-Finnish) population ofthe Genome Aggregation Database, though this is based on one allele in a region of good sequencing coverage so the variant is presumed to be rare. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Labcorp Genetics |
RCV003768442 | SCV004641009 | pathogenic | not provided | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly1831Aspfs*18) 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 present in population databases (rs747371923, gnomAD 0.007%). 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: 632272). For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV004745584 | SCV005365828 | likely pathogenic | MYO15A-related disorder | 2024-06-20 | no assertion criteria provided | clinical testing | The MYO15A c.5492delG variant is predicted to result in a frameshift and premature protein termination (p.Gly1831Aspfs*18). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in MYO15A are expected to be pathogenic. This variant is interpreted as likely pathogenic. |