Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000814776 | SCV000955201 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with lysine at codon 190 of the FKTN protein (p.Arg190Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is present in population databases (rs760967116, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with FKTN-related conditions. 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 | RCV003166338 | SCV003857384 | uncertain significance | Cardiovascular phenotype | 2023-02-16 | criteria provided, single submitter | clinical testing | The p.R190K variant (also known as c.569G>A), located in coding exon 4 of the FKTN gene, results from a G to A substitution at nucleotide position 569. The arginine at codon 190 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |