Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002028780 | SCV002294830 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 1583 of the FLNC protein (p.Gly1583Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FLNC-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV003170565 | SCV003856287 | uncertain significance | Cardiovascular phenotype | 2022-12-18 | criteria provided, single submitter | clinical testing | The p.G1583S variant (also known as c.4747G>A), located in coding exon 28 of the FLNC gene, results from a G to A substitution at nucleotide position 4747. The glycine at codon 1583 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. |