ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.1712G>A (p.Arg571His)

dbSNP: rs1368149283
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727492 SCV000619827 uncertain significance not provided 2017-08-10 criteria provided, single submitter clinical testing The R553H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R553H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function.
Eurofins Ntd Llc (ga) RCV000727492 SCV000709101 uncertain significance not provided 2017-06-06 criteria provided, single submitter clinical testing
Invitae RCV001232730 SCV001405298 uncertain significance Qualitative or quantitative defects of dysferlin 2022-05-20 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 553 of the DYSF protein (p.Arg553His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 451164). 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.
Natera, Inc. RCV001829509 SCV002079823 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2B 2020-08-04 no assertion criteria provided clinical testing

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