ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.3176G>A (p.Arg1059His)

gnomAD frequency: 0.00002  dbSNP: rs754763074
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000592866 SCV000704341 uncertain significance not provided 2018-04-20 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001563740 SCV001786748 uncertain significance Miyoshi muscular dystrophy 1 2021-07-14 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001563741 SCV001786749 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2B 2021-07-14 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001563742 SCV001786750 uncertain significance Distal myopathy with anterior tibial onset 2021-07-14 criteria provided, single submitter clinical testing
Invitae RCV001854033 SCV002310883 likely pathogenic Qualitative or quantitative defects of dysferlin 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1041 of the DYSF protein (p.Arg1041His). This variant is present in population databases (rs754763074, gnomAD 0.01%). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 30564623). ClinVar contains an entry for this variant (Variation ID: 499041). 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 80%. This variant disrupts the p.Arg1041 amino acid residue in DYSF. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15469449, 33610434). 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 RCV000592866 SCV004234439 uncertain significance not provided 2023-02-27 criteria provided, single submitter clinical testing

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