ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.5727G>T (p.Arg1909Ser)

dbSNP: rs1336670524
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001004987 SCV001164538 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2B 2018-12-03 criteria provided, single submitter research The heterozygous p.Arg1909Ser variant in DYSF was identified by our study in the compound heterozygous state, with a VUS, in one individual with limb-girdle muscular dystrophy (LGMD). This variant was absent from large population studies and computational prediction tools suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg1909Ser variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3 (Richards 2015).
Labcorp Genetics (formerly Invitae), Labcorp RCV001860571 SCV002131243 likely pathogenic Qualitative or quantitative defects of dysferlin 2024-05-20 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 1870 of the DYSF protein (p.Arg1870Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 813990). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DYSF protein function with a positive predictive value of 95%. 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.

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