Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000696525 | SCV000825089 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2109 of the FLNC protein (p.Ile2109Val). This variant is present in population databases (rs755736125, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 574563). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine 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 | RCV002360774 | SCV002658381 | uncertain significance | Cardiovascular phenotype | 2023-06-02 | criteria provided, single submitter | clinical testing | The p.I2109V variant (also known as c.6325A>G), located in coding exon 38 of the FLNC gene, results from an A to G substitution at nucleotide position 6325. The isoleucine at codon 2109 is replaced by valine, an amino acid with highly similar properties. This variant has been detected in an arrhythmogenic cardiomyopathy cohort; however, details were not provided (Celeghin R et al. Heart Rhythm. 2022 Feb;19(2):235-243). This amino acid position is not well 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. |