Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000528480 | SCV000651171 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2017-01-03 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FLNC-related disease. This sequence change replaces alanine with aspartic acid at codon 2537 of the FLNC protein (p.Ala2537Asp). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and aspartic acid. |
| Gene |
RCV003126816 | SCV003803497 | uncertain significance | not provided | 2022-07-22 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV004024200 | SCV005017819 | uncertain significance | Cardiovascular phenotype | 2024-01-29 | criteria provided, single submitter | clinical testing | The p.A2537D variant (also known as c.7610C>A), located in coding exon 46 of the FLNC gene, results from a C to A substitution at nucleotide position 7610. The alanine at codon 2537 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |