Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002015602 | SCV002297022 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-11-20 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 703 of the FLNC protein (p.Lys703Arg). |
| Ambry Genetics | RCV002423225 | SCV002724598 | uncertain significance | Cardiovascular phenotype | 2021-05-24 | criteria provided, single submitter | clinical testing | The p.K703R variant (also known as c.2108A>G), located in coding exon 13 of the FLNC gene, results from an A to G substitution at nucleotide position 2108. The lysine at codon 703 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is 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. |