ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.6238C>T (p.Arg2080Trp)

gnomAD frequency: 0.00005  dbSNP: rs200990851
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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) RCV000724069 SCV000231345 uncertain significance not provided 2014-10-21 criteria provided, single submitter clinical testing
GeneDx RCV000724069 SCV000620121 uncertain significance not provided 2017-08-18 criteria provided, single submitter clinical testing The R2041W variant in the DYSF gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R2041W 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. In addition, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R2041W as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001852228 SCV002128326 uncertain significance Qualitative or quantitative defects of dysferlin 2022-01-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2041 of the DYSF protein (p.Arg2041Trp). This variant is present in population databases (rs200990851, gnomAD 0.005%). 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: 197966). 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. 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.
Revvity Omics, Revvity RCV000724069 SCV004234433 uncertain significance not provided 2023-04-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV004020137 SCV004861698 uncertain significance Inborn genetic diseases 2023-12-15 criteria provided, single submitter clinical testing The c.6121C>T (p.R2041W) alteration is located in exon 54 (coding exon 54) of the DYSF gene. This alteration results from a C to T substitution at nucleotide position 6121, causing the arginine (R) at amino acid position 2041 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001833085 SCV002080358 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2B 2020-02-21 no assertion criteria provided clinical testing

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