ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.7972G>A (p.Val2658Met)

gnomAD frequency: 0.00002  dbSNP: rs1269145751
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000559964 SCV000651182 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2658 of the FLNC protein (p.Val2658Met). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 472185). 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) performed at Invitae indicates that this missense variant is not expected to disrupt FLNC protein function with a negative predictive value of 80%. 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.
AiLife Diagnostics, AiLife Diagnostics RCV002223225 SCV002501662 uncertain significance not provided 2021-07-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002420502 SCV002676489 uncertain significance Cardiovascular phenotype 2022-10-27 criteria provided, single submitter clinical testing The p.V2658M variant (also known as c.7972G>A), located in coding exon 47 of the FLNC gene, results from a G to A substitution at nucleotide position 7972. The valine at codon 2658 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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