ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.3190C>T (p.Arg1064Cys)

gnomAD frequency: 0.00004  dbSNP: rs752810646
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518215 SCV000613197 uncertain significance not specified 2016-10-05 criteria provided, single submitter clinical testing
Invitae RCV001239622 SCV001412508 likely pathogenic Qualitative or quantitative defects of dysferlin 2023-11-17 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 1046 of the DYSF protein (p.Arg1046Cys). This variant is present in population databases (rs752810646, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DYSF-related conditions. ClinVar contains an entry for this variant (Variation ID: 447285). 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%. This variant disrupts the p.Arg1046 amino acid residue in DYSF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11468312, 18853459, 25591676, 27647186). This suggests that this residue is clinically significant, and that variants that disrupt this residue 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.
Revvity Omics, Revvity RCV003144306 SCV003831284 uncertain significance not provided 2019-07-12 criteria provided, single submitter clinical testing
GeneDx RCV003144306 SCV003837186 uncertain significance not provided 2023-03-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24438169)
Natera, Inc. RCV001834664 SCV002082264 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2B 2019-10-28 no assertion criteria provided clinical testing

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