Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Revvity Omics, |
RCV001781198 | SCV002024431 | likely pathogenic | not provided | 2019-05-10 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001851715 | SCV002247204 | pathogenic | Qualitative or quantitative defects of dysferlin | 2023-09-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in altered splicing, which introduces a frameshift and introduces a premature termination codon (PMID: 10766988). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 6672). This variant is also known as a G to A bp alteration that is predicted to affect position 5 in the intron following amino acid 1686. This variant has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 10766988). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs745891180, gnomAD 0.006%). This sequence change falls in intron 45 of the DYSF gene. It does not directly change the encoded amino acid sequence of the DYSF protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298436 | SCV002598752 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy | 2022-09-26 | criteria provided, single submitter | clinical testing | Variant summary: DYSF c.5057+5G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: one predicts the variant abolishes a 5 splicing donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing. The variant allele was found at a frequency of 8e-06 in 251286 control chromosomes. c.5057+5G>A has been reported in the literature in multiple individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive. These data indicate that the variant is very likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV003466824 | SCV004194223 | likely pathogenic | Miyoshi muscular dystrophy 1 | 2023-09-02 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000007057 | SCV000027253 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2000-04-10 | no assertion criteria provided | literature only |