ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.4060C>G (p.Arg1354Gly)

gnomAD frequency: 0.00001  dbSNP: rs138193236
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000691278 SCV000819030 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2024-12-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1354 of the FLNC protein (p.Arg1354Gly). This variant is present in population databases (rs138193236, gnomAD 0.005%). 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: 570414). Invitae Evidence 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 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.
Revvity Omics, Revvity RCV003144512 SCV003831406 uncertain significance not provided 2023-05-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV004025083 SCV005017735 uncertain significance Cardiovascular phenotype 2023-11-21 criteria provided, single submitter clinical testing The p.R1354G variant (also known as c.4060C>G), located in coding exon 23 of the FLNC gene, results from a C to G substitution at nucleotide position 4060. The arginine at codon 1354 is replaced by glycine, an amino acid with dissimilar properties. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV003144512 SCV005409372 uncertain significance not provided 2024-05-21 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003965441 SCV004778873 uncertain significance FLNC-related disorder 2023-12-04 no assertion criteria provided clinical testing The FLNC c.4060C>G variant is predicted to result in the amino acid substitution p.Arg1354Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0051% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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