Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000649108 | SCV000770933 | likely benign | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-12-17 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002360621 | SCV002661711 | uncertain significance | Cardiovascular phenotype | 2022-03-24 | criteria provided, single submitter | clinical testing | The p.K2260R variant (also known as c.6779A>G), located in coding exon 41 of the FLNC gene, results from an A to G substitution at nucleotide position 6779. The lysine at codon 2260 is replaced by arginine, an amino acid with highly similar properties. This alteration has been seen in family members of an individual who was noted to have a post mortem diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) after sudden cardiac death (Hall CL et al. Int J Cardiol, 2020 05;307:101-108). This amino acid position is not well conserved in available vertebrate species, and arginine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV003144438 | SCV003833185 | uncertain significance | not provided | 2020-07-15 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV003144438 | SCV004161048 | likely benign | not provided | 2022-09-01 | criteria provided, single submitter | clinical testing | FLNC: BP4 |
| New York Genome Center | RCV003448330 | SCV004176072 | uncertain significance | Hypertrophic cardiomyopathy 26 | 2023-08-09 | criteria provided, single submitter | clinical testing | The c.6779A>G, p.(Lys2260Arg) variant identified in the FLNC gene is a missense variant predicted to substitute a Lysine for Arginine at amino acid 2260/2762 (exon 41/48). This variant is found with low frequency in population databases (gnomADv2.1.1, gnomADv3.1.2, BRAVO-TOPMed, All of US; allele frequency: <0.0001, 0 homozygotes) suggesting it is not a common benign variant in the populations represented in those databases. The c.6779A>G, p.(Lys2260Arg) variant has been reported in ClinVar as both a Variant of Uncertain Significance and Likely Benign (VarID: 539380), and to our current knowledge has not been reported in affected individuals in the literature. Given the lack of compelling evidence for its pathogenicity, the c.6779A>G, p.(Lys2260Arg) variant identified in the FLNC gene is reported as a Variant of Uncertain Significance. |