Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001207187 | SCV001378529 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2019-09-12 | 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: "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). This sequence change replaces valine with leucine at codon 2288 of the FLNC protein (p.Val2288Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. |
| Ambry Genetics | RCV002365935 | SCV002665559 | uncertain significance | Cardiovascular phenotype | 2021-04-13 | criteria provided, single submitter | clinical testing | The p.V2288L variant (also known as c.6862G>C), located in coding exon 41 of the FLNC gene, results from a G to C substitution at nucleotide position 6862. The valine at codon 2288 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available 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. |