Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000823305 | SCV000964159 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2018-10-06 | criteria provided, single submitter | clinical testing | 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FLNC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 437 of the FLNC protein (p.Arg437Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. |
| Ambry Genetics | RCV003307561 | SCV004004592 | uncertain significance | Cardiovascular phenotype | 2023-03-23 | criteria provided, single submitter | clinical testing | The p.R437G variant (also known as c.1309C>G), located in coding exon 8 of the FLNC gene, results from a C to G substitution at nucleotide position 1309. The arginine at codon 437 is replaced by glycine, an amino acid with dissimilar 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. |