Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001254696 | SCV001430762 | likely pathogenic | Limb-girdle muscular dystrophy | 2020-05-29 | criteria provided, single submitter | research | The p.Arg88Ter variant in BVES was identified by our study in 1 homozygous individual with limb-girdle muscular dystrophy (PMID:31119192). Data from large population studies is insufficient to assess the frequency of this variant. This nonsense variant leads to a premature termination codon at position 88, which is predicted to lead to a truncated or absent protein. While there is some evidence to suggest that loss of function of the BVES gene is a disease mechanism in autosomal recessive limb girdle muscular dystrophy, this association is not yet strongly established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). In vitro functional studies provide some evidence that the p.Arg88Ter variant may slightly impact protein function (PMID:31119192). However, these types of assays may not accurately represent biological function. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM3_supporting, PS3_moderate, PVS1_strong (Richards 2015). |
Gene |
RCV003314643 | SCV004014279 | pathogenic | not provided | 2023-01-09 | criteria provided, single submitter | clinical testing | Nonsense 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 significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35660068, 34940515, 27397505, 35718670, 31817925, 33310206, 32684383, 32528171, 31119192) |
OMIM | RCV000768555 | SCV000899254 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2X | 2022-08-25 | no assertion criteria provided | literature only |