ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.4021C>G (p.Gln1341Glu) (rs147950418)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000658869 SCV000333048 uncertain significance not provided 2015-07-14 criteria provided, single submitter clinical testing
GeneDx RCV000177909 SCV000568714 uncertain significance not specified 2017-03-02 criteria provided, single submitter clinical testing The Q1323E variant was previously reported as a variant of uncertain significance in a patient with cerebellar ataxia who harbored additional variants in another gene associated with ataxia (Fogel et al., 2014). The Q1323E variant is observed in 74/66236 (0.11%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species; however, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with DYSF-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000658869 SCV000780668 uncertain significance not provided 2017-12-01 criteria provided, single submitter clinical testing
Invitae RCV000691904 SCV000819703 uncertain significance Dysferlinopathy 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces glutamine with glutamic acid at codon 1323 of the DYSF protein (p.Gln1323Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs147950418, ExAC 0.2%). This variant has been observed in combination with another DYSF variant in a family affected with Limb-Girdle Muscular Dystrophy or LGMD (PMID: 29970176). ClinVar contains an entry for this variant (Variation ID: 197004). 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: "Tolerated"; PolyPhen-2: "Possibly 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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