ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.318C>G (p.Phe106Leu)

gnomAD frequency: 0.00004  dbSNP: rs886037829
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001394421 SCV001596105 likely benign Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2024-01-28 criteria provided, single submitter clinical testing
GeneDx RCV001555793 SCV001777260 uncertain significance not provided 2021-04-19 criteria provided, single submitter clinical testing Identified in a boy with dysmorphic features and dilated cardiomyopathy (DCM), and in his brother with DCM, both of whom harbored an additional FLNC nonsense variant on the opposite allele; multiple adults harboring only the F106L variant were asymptomatic (Reinstein et al., 2016); Published functional studies demonstrate decreased FLNC protein expression (Reinstein et al., 2016), however, further studies are needed to validate the functional effect of this variant in vivo; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32112656, 32154132, 27601210)
Ambry Genetics RCV002321943 SCV002609387 uncertain significance Cardiovascular phenotype 2023-02-02 criteria provided, single submitter clinical testing The p.F106L variant (also known as c.318C>G), located in coding exon 1 of the FLNC gene, results from a C to G substitution at nucleotide position 318. The phenylalanine at codon 106 is replaced by leucine, an amino acid with highly similar properties. This variant was reported in two brothers with early onset dilated cardiomyopathy and additional features who also had an FLNC truncating variant. Four family members with only the p.F106L alteration were unaffected and had normal echocardiograms (Reinstein E et al. Eur. J. Hum. Genet., 2016 12;24:1792-1796). Limited studies in rat cardiomyocytes showed some functional impact (Reinstein E et al. Eur. J. Hum. Genet., 2016 12;24:1792-1796). 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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