Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001316094 | SCV001506697 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 2614 of the FLNC protein (p.Val2614Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with FLNC-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV002412014 | SCV002669286 | uncertain significance | Cardiovascular phenotype | 2023-11-23 | criteria provided, single submitter | clinical testing | The p.V2614M variant (also known as c.7840G>A), located in coding exon 47 of the FLNC gene, results from a G to A substitution at nucleotide position 7840. The valine at codon 2614 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |