Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001895845 | SCV002154654 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-10-03 | 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 2340 of the FLNC protein (p.Arg2340Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. |
Ambry Genetics | RCV002361160 | SCV002666901 | uncertain significance | Cardiovascular phenotype | 2019-07-31 | criteria provided, single submitter | clinical testing | The p.R2340W variant (also known as c.7018C>T), located in coding exon 42 of the FLNC gene, results from a C to T substitution at nucleotide position 7018. The arginine at codon 2340 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
Prevention |
RCV003407891 | SCV004112168 | uncertain significance | FLNC-related disorder | 2023-04-25 | criteria provided, single submitter | clinical testing | The FLNC c.7018C>T variant is predicted to result in the amino acid substitution p.Arg2340Trp. This variant was reported in an individual with hypertrophic cardiomyopathy and left ventricular hypertrabeculation. Functional studies showed that this variant does not alter subcellular localization of the FLNC protein (Bermúdez-Jiménez et al. 2023. PubMed ID: 35952944). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |