ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.5557C>T (p.Arg1853Cys)

gnomAD frequency: 0.00001  dbSNP: rs1280185461
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673454 SCV000798658 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2B 2018-03-16 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001141004 SCV001301317 uncertain significance Qualitative or quantitative defects of dysferlin 2017-11-19 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001141004 SCV003524776 pathogenic Qualitative or quantitative defects of dysferlin 2023-11-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1814 of the DYSF protein (p.Arg1814Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with DYSF-related conditions (PMID: 21522182, 26404900). ClinVar contains an entry for this variant (Variation ID: 557327). 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%. 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.

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