Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001004961 | SCV001164498 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2018-12-03 | criteria provided, single submitter | research | The heterozygous p.Gln1608Ter variant in DYSF was identified by our study in the compound heterozygous state, with a VUS, in one individual with limb-girdle muscular dystrophy (LGMD) This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1608, which is predicted to lead to a truncated or absent protein. Loss of function of the DYSF gene is an established disease mechanism in autosomal recessive LGMD. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1 (Richards 2015). |
Invitae | RCV001862745 | SCV002188656 | pathogenic | Qualitative or quantitative defects of dysferlin | 2022-12-14 | 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: 813970). This variant has not been reported in the literature in individuals affected with DYSF-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1569*) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). |