Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000814849 | SCV000955280 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-06-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2173 of the FLNC protein (p.Arg2173Cys). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 658104). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (rs767250474, gnomAD 0.0009%). |
| Ambry Genetics | RCV004028830 | SCV005018236 | uncertain significance | Cardiovascular phenotype | 2023-12-15 | criteria provided, single submitter | clinical testing | The p.R2173C variant (also known as c.6517C>T), located in coding exon 40 of the FLNC gene, results from a C to T substitution at nucleotide position 6517. The arginine at codon 2173 is replaced by cysteine, an amino acid with highly 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. |