Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000649138 | SCV000770963 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2022-03-29 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs757887021, gnomAD 0.006%). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 539408). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 391 of the FLNC protein (p.Val391Met). |
| Ambry Genetics | RCV002331236 | SCV002632124 | uncertain significance | Cardiovascular phenotype | 2024-02-23 | criteria provided, single submitter | clinical testing | The p.V391M variant (also known as c.1171G>A), located in coding exon 7 of the FLNC gene, results from a G to A substitution at nucleotide position 1171. The valine at codon 391 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |