Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000382100 | SCV000344712 | pathogenic | not provided | 2016-08-18 | criteria provided, single submitter | clinical testing | |
Foundation for Research in Genetics and Endocrinology, |
RCV001172377 | SCV001190520 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2020-03-20 | criteria provided, single submitter | clinical testing | A homozygous 3' splice site variation in intron 22 of the DYSF gene that affects the invariant AG acceptor splice site upstream of exon 23 was detected. The observed variant c.2217-1G>T has not been reported in the 1000 genomes and ExAC databases. The variant has previously been reported as c.2163-1G>T, in homozygous state in a patient affected with limb-girdle muscular dystrophy-2B (Klinge L et al. 2010). The in silico prediction of the variant is damaging by MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic. |
Invitae | RCV003574729 | SCV004292564 | pathogenic | Qualitative or quantitative defects of dysferlin | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 22 of the DYSF gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). This variant is present in population databases (no rsID available, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with limb-girdle muscular dystrophy type 2 (PMID: 19528035, 30564623). ClinVar contains an entry for this variant (Variation ID: 290204). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |