Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Myriad Genetics, |
RCV001264130 | SCV001442231 | likely pathogenic | Miyoshi muscular dystrophy 1; Autosomal recessive limb-girdle muscular dystrophy type 2B; Distal myopathy with anterior tibial onset | 2019-02-26 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001389481 | SCV001590872 | pathogenic | Qualitative or quantitative defects of dysferlin | 2020-01-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with DYSF-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu1454*) in the DYSF gene. It is expected to result in an absent or disrupted protein product. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226456 | SCV003922899 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy | 2023-03-02 | criteria provided, single submitter | clinical testing | Variant summary: DYSF c.4360G>T (p.Glu1454X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250342 control chromosomes (gnomAD). c.4360G>T has been reported in the literature in individuals affected with dysferlinopathy (example: Harris_2016 and Fernandez-Eulate_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV004570655 | SCV005060280 | pathogenic | Miyoshi muscular dystrophy 1 | 2024-01-17 | criteria provided, single submitter | clinical testing |