Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000223613 | SCV000271417 | pathogenic | Rare genetic deafness | 2016-01-03 | criteria provided, single submitter | clinical testing | The p.Arg939fs variant in MYO6 has been previously reported in 1 individual with nonsyndromic hearing loss and was found to segregate with disease in 14 affecte d family members in an autosomal dominant manner (Cheng 2014). It has also been identified in 1/66162 European chromosomes by the Exome Aggregation Consortium ( ExAC, http://exac.broadinstitute.org). This variant is predicted to cause a fram eshift, which alters the protein?s amino acid sequence beginning at position 939 and lead to a premature termination codon 2 amino acids downstream. This altera tion is then predicted to lead to a truncated or absent protein. Truncating or l oss-of-function variants in the MYO6 gene have been associated with autosomal re cessive congenital sensorineural hearing loss (Ahmed 2003) as well as autosomal dominant postlingual/late-onset progressive sensorineural hearing loss with vari able onset and severity (Hilgert 2008, Sanggaard 2008, Neveling 2013, Schrauwen 2013, Volk 2013). In summary, this variant meets our criteria to be classified a s pathogenic for dominantly inherited nonsyndromic hearing loss based upon the s egregation studies in the reported family and its predicted impact to the protei n. |
Gene |
RCV001570042 | SCV001794238 | pathogenic | not provided | 2022-11-15 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25227905) |
Labcorp Genetics |
RCV001570042 | SCV002240361 | pathogenic | not provided | 2022-07-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 228375). This premature translational stop signal has been observed in individual(s) with deafness (PMID: 25227905). This variant is present in population databases (rs753233152, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg939Thrfs*2) in the MYO6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO6 are known to be pathogenic (PMID: 12687499, 18348273, 23767834, 25999546, 30582396). For these reasons, this variant has been classified as Pathogenic. |