ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.803A>C (p.Asn268Thr) (rs150917600)

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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 RCV000656845 SCV000232175 uncertain significance not provided 2017-04-03 criteria provided, single submitter clinical testing
GeneDx RCV000656845 SCV000582250 uncertain significance not provided 2018-04-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DYSF gene. The N236T variant has notbeen published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 35/24016 (0.15%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). The N236T variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000706741 SCV000835810 uncertain significance Dysferlinopathy 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces asparagine with threonine at codon 236 of the DYSF protein (p.Asn236Thr). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and threonine. This variant is present in population databases (rs150917600, ExAC 0.1%). This variant has not been reported in the literature in individuals with DYSF-related disease. ClinVar contains an entry for this variant (Variation ID: 198494). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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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