ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.4078C>T (p.Arg1360Trp) (rs199870606)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000408314 SCV000329869 pathogenic not provided 2016-09-21 criteria provided, single submitter clinical testing The R1342W pathogenic variant in the DYSF gene has been reported previously in an individual with a phenotype consistent with dysferlinopathy who also possessed a second variant in the DYSF gene (Cacciottolo et al., 2011). Western blot on muscle tissue from this individual demonstrated complete absence of dysferlin expression (Cacciottolo et al., 2011). The R1342W variant is a non-conservative amino acid substitution that occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The R1342W variant was not observed at a significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R1342W as a pathogenic variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000408314 SCV000338266 uncertain significance not provided 2015-12-17 criteria provided, single submitter clinical testing
Invitae RCV000802767 SCV000942610 uncertain significance Dysferlinopathy 2018-08-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1342 of the DYSF protein (p.Arg1342Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs199870606, ExAC 0.05%). This variant has been observed in an individual affected with dysferlinopathy (PMID: 21522182, 22616201). ClinVar contains an entry for this variant (Variation ID: 280068). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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