Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002012652 | SCV002280463 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with valine at codon 419 of the FKTN protein (p.Ile419Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). 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 | RCV002423211 | SCV002680865 | uncertain significance | Cardiovascular phenotype | 2021-09-23 | criteria provided, single submitter | clinical testing | The p.I419V variant (also known as c.1255A>G), located in coding exon 9 of the FKTN gene, results from an A to G substitution at nucleotide position 1255. The isoleucine at codon 419 is replaced by valine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |