Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479599 | SCV000573900 | uncertain significance | not provided | 2018-08-30 | criteria provided, single submitter | clinical testing | The K510Q variant of uncertain significance in the FLNC gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 5/246044 (0.002%) alleles from individuals of multiple ethnic backgrounds in large population cohorts (Lek et al., 2016). The K510Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
| Invitae | RCV000812939 | SCV000953269 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-04-06 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 424119). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 510 of the FLNC protein (p.Lys510Gln). |
| Ambry Genetics | RCV002395180 | SCV002708232 | uncertain significance | Cardiovascular phenotype | 2022-10-28 | criteria provided, single submitter | clinical testing | The p.K510Q variant (also known as c.1528A>C), located in coding exon 9 of the FLNC gene, results from an A to C substitution at nucleotide position 1528. The lysine at codon 510 is replaced by glutamine, an amino acid with similar properties. 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. |