ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.6241C>T (p.Arg2081Cys) (rs121908955)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000007052 SCV000789624 likely pathogenic Limb-girdle muscular dystrophy, type 2B 2017-02-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000080320 SCV000333451 pathogenic not provided 2015-08-04 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne RCV000007052 SCV000803828 likely pathogenic Limb-girdle muscular dystrophy, type 2B 2017-11-07 criteria provided, single submitter clinical testing
GeneDx RCV000080320 SCV000321574 pathogenic not provided 2018-05-01 criteria provided, single submitter clinical testing The R2042C pathogenic variant in the DYSF gene has been reported previously with limb-girdle muscular dystrophy 2B or Miyoshi myopathy, in affected individuals who were heterozygous with another pathogenic variant or affected individuals with no second variant identified (Szymanska et al., 2014; Krahn et al., 2009; Kesari et al., 2008; Cagliani et al., 2005; Liu et al., 1998). The R2042C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R2042C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R2042C as a pathogenic variant.
Invitae RCV000815134 SCV000955580 pathogenic Dysferlinopathy 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 2042 of the DYSF protein (p.Arg2042Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs121908955, ExAC 0.009%). This variant has been observed in individual(s) with limb-girdle muscular dystrophy and Miyoshi myopathy (PMID: 16100712, 17698709, 22194990, 25574751, 27666772). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 6668). This variant has been reported to affect DYSF protein function (PMID: 27641898). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007051 SCV000027247 pathogenic Miyoshi muscular dystrophy 1 1998-09-01 no assertion criteria provided literature only
OMIM RCV000007052 SCV000809052 pathogenic Limb-girdle muscular dystrophy, type 2B 1998-09-01 no assertion criteria provided literature only

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