Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001927794 | SCV002173367 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 274 of the FKTN protein (p.Arg274Gln). This variant is present in population databases (rs767503045, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FKTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1404650). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Revvity Omics, |
RCV003146332 | SCV003832697 | uncertain significance | not provided | 2019-05-21 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004042629 | SCV005037360 | uncertain significance | Cardiovascular phenotype | 2024-01-17 | criteria provided, single submitter | clinical testing | The p.R274Q variant (also known as c.821G>A), located in coding exon 6 of the FKTN gene, results from a G to A substitution at nucleotide position 821. The arginine at codon 274 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |