Total submissions: 3
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 | |
Gene |
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. |