Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000498262 | SCV000589421 | uncertain significance | not provided | 2016-03-01 | criteria provided, single submitter | clinical testing | The K901N variant in the FLNC gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The K901N variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K901N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs in the Filamin 7 region at a position in the gene that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, we interpret K901N as a variant of unknown significance |
Invitae | RCV001857001 | SCV002178563 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-06-21 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 901 of the FLNC protein (p.Lys901Asn). This variant is not present in population databases (gnomAD no frequency). 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: 431863). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. 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 | RCV003278846 | SCV004006261 | uncertain significance | Cardiovascular phenotype | 2023-05-21 | criteria provided, single submitter | clinical testing | The p.K901N variant (also known as c.2703G>T), located in coding exon 18 of the FLNC gene, results from a G to T substitution at nucleotide position 2703. The lysine at codon 901 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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. |
Revvity Omics, |
RCV000498262 | SCV004234823 | uncertain significance | not provided | 2023-04-25 | criteria provided, single submitter | clinical testing |