Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000726915 | SCV000573342 | uncertain significance | not provided | 2017-02-16 | criteria provided, single submitter | clinical testing | The G1651D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G1651D variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with FLNC-related disorders (Stenson et al., 2014). |
Eurofins Ntd Llc |
RCV000726915 | SCV000704142 | uncertain significance | not provided | 2016-11-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001215135 | SCV001386863 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1651 of the FLNC protein (p.Gly1651Asp). This variant is present in population databases (rs762493974, gnomAD 0.04%). 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 423624). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. |
Ambry Genetics | RCV002341149 | SCV002642868 | uncertain significance | Cardiovascular phenotype | 2019-08-06 | criteria provided, single submitter | clinical testing | The p.G1651D variant (also known as c.4952G>A) is located in coding exon 30 of the FLNC gene. The glycine at codon 1651 is replaced by aspartic acid, an amino acid with similar properties. This change occurs in the first base pair of coding exon 30. This amino acid position is highly conserved in available vertebrate species. 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. |
Revvity Omics, |
RCV000726915 | SCV003833111 | uncertain significance | not provided | 2019-11-16 | criteria provided, single submitter | clinical testing |