ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.6518G>A (p.Arg2173His)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002364198 SCV002659216 uncertain significance Cardiovascular phenotype 2023-07-12 criteria provided, single submitter clinical testing The p.R2173H variant (also known as c.6518G>A), located in coding exon 40 of the FLNC gene, results from a G to A substitution at nucleotide position 6518. The arginine at codon 2173 is replaced by histidine, an amino acid with highly similar properties. This variant has been detected in a dilated cardiomyopathy cohorts; however, details were not provided (Verdonschot JAJ et al. Hum. Mutat., 2020 Jun;41:1091-1111; Mori V et al. Int J Cardiol Heart Vasc. 2022 Jun;40:101023). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV003098275 SCV002939246 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2022-01-05 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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 missense change has been observed in individual(s) with clinical features of FLNC-related conditions (PMID: 32112656). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2173 of the FLNC protein (p.Arg2173His).
Revvity Omics, Revvity RCV003146546 SCV003833038 uncertain significance not provided 2022-03-08 criteria provided, single submitter clinical testing

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