Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001379106 | SCV001576840 | likely pathogenic | Qualitative or quantitative defects of dysferlin | 2021-08-04 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 55 of the DYSF gene. The 5' boundary is likely confined to intron 54. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. A similar copy number variant has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 19594366). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the DYSF protein in which other variant(s) (p.Met2073Val) have been observed in individuals with DYSF-related conditions (PMID: 17129727). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |