ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.5431C>T (p.Arg1811Trp)

gnomAD frequency: 0.00005  dbSNP: rs374794518
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001233369 SCV001405959 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2023-12-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1811 of the FLNC protein (p.Arg1811Trp). This variant is present in population databases (rs374794518, gnomAD 0.02%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 959931). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. 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.
GeneDx RCV001546048 SCV001765495 uncertain significance not provided 2020-04-13 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Ambry Genetics RCV002348785 SCV002652916 uncertain significance Cardiovascular phenotype 2023-08-13 criteria provided, single submitter clinical testing The p.R1811W variant (also known as c.5431C>T), located in coding exon 33 of the FLNC gene, results from a C to T substitution at nucleotide position 5431. The arginine at codon 1811 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is well 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.
Fulgent Genetics, Fulgent Genetics RCV002497797 SCV002806960 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26 2022-02-17 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001546048 SCV003831424 uncertain significance not provided 2022-02-01 criteria provided, single submitter clinical testing

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