Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001059658 | SCV001224287 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1778 of the FLNC protein (p.Met1778Val). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 854577). 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. 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. |
Ambry Genetics | RCV002348434 | SCV002640805 | uncertain significance | Cardiovascular phenotype | 2019-08-14 | criteria provided, single submitter | clinical testing | The p.M1778V variant (also known as c.5332A>G), located in coding exon 32 of the FLNC gene, results from an A to G substitution at nucleotide position 5332. The methionine at codon 1778 is replaced by valine, an amino acid with highly similar properties. This variant has been detected in a healthy control cohort (Cui H et al. Mol Genet Genomic Med, 2018 11;6:1104-1113). This amino acid position is not 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. |