ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.4904A>G (p.Asn1635Ser) (rs772664716)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726189 SCV000342735 uncertain significance not provided 2018-04-25 criteria provided, single submitter clinical testing
GeneDx RCV000726189 SCV000576843 uncertain significance not provided 2017-04-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DYSF gene. The N1596S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N1596S variant is observed in 6/6612 (0.09%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N1596S 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000647992 SCV000769802 uncertain significance Dysferlinopathy 2018-11-02 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 1596 of the DYSF protein (p.Asn1596Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs772664716, ExAC 0.09%). This variant has not been reported in the literature in individuals with DYSF-related disease. ClinVar contains an entry for this variant (Variation ID: 288577). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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