ClinVar Miner

Submissions for variant NM_001458.4(FLNC):c.4952G>A (p.Gly1651Asp) (rs762493974)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000726915 SCV000573342 uncertain significance not provided 2017-02-16 criteria provided, single submitter clinical testing The G1651D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G1651D 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). This 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. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with FLNC-related disorders (Stenson et al., 2014).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726915 SCV000704142 uncertain significance not provided 2016-11-30 criteria provided, single submitter clinical testing
Invitae RCV001215135 SCV001386863 uncertain significance Myofibrillar myopathy, filamin C-related; Myopathy, distal, 4; Cardiomyopathy, familial hypertrophic, 26; Dilated Cardiomyopathy, Dominant 2019-04-19 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 1651 of the FLNC protein (p.Gly1651Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs762493974, ExAC 0.03%). This variant has not been reported in the literature in individuals with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 423624). 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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