ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.6539G>A (p.Arg2180His)

dbSNP: rs1554401209
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001070374 SCV001235600 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2019-03-12 criteria provided, single submitter clinical testing 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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FLNC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with histidine at codon 2180 of the FLNC protein (p.Arg2180His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine.
Ambry Genetics RCV002365778 SCV002661241 uncertain significance Cardiovascular phenotype 2022-09-27 criteria provided, single submitter clinical testing The p.R2180H variant (also known as c.6539G>A), located in coding exon 40 of the FLNC gene, results from a G to A substitution at nucleotide position 6539. The arginine at codon 2180 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in a pediatric dilated cardiomyopathy cohort (Khan RS et al. J Am Heart Assoc, 2022 01;11:e022854). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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