Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000605133 | SCV000713729 | pathogenic | Rare genetic deafness | 2017-10-26 | criteria provided, single submitter | clinical testing | The p.Arg849X variant in MYO6 has been reported in 1 individual with nonsyndromi c hearing loss and segregated with disease in at least 14 affected relatives in an autosomal dominant manner (Sanggaard 2008). This variant has been identified in 1/17246 of East Asian chromosomes and 1/111636 European chromosomes by the Ge nome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs121 912561). This nonsense variant leads to a premature termination codon at positio n 849, which is predicted to lead to a truncated or absent protein. Truncating o r loss-of-function variants in the MYO6 gene have been associated with autosomal recessive congenital sensorineural hearing loss (Ahmed 2003) as well as autosom al dominant postlingual/late-onset progressive sensorineural hearing loss with v ariable onset and severity (Hilgert 2008, Sanggaard 2008, Neveling 2013, Schrauw en 2013, Volk 2013). In summary, this variant meets criteria to be classified as pathogenic for nonsyndromic hearing loss in an autosomal dominant manner based upon the segregation studies in the reported family and its predicted impact to the protein. ACMG/AMP Criteria applied: PVS1, PP1_S, PS4(Richards 2015). |
| Invitae | RCV003555982 | SCV004294627 | pathogenic | not provided | 2023-07-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 8582). This sequence change creates a premature translational stop signal (p.Arg849*) 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). This variant is present in population databases (rs121912561, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with clinical features of MYO6-related conditions (PMID: 18348273, 33297549). |
| OMIM | RCV000009113 | SCV000029330 | pathogenic | Autosomal dominant nonsyndromic hearing loss 22 | 2008-04-15 | no assertion criteria provided | literature only |