Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000647452 | SCV000769248 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2020-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with leucine at codon 59 of the ALK protein (p.Val59Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ALK-related disease. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002397271 | SCV002711726 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-24 | criteria provided, single submitter | clinical testing | The p.V59L variant (also known as c.175G>T), located in coding exon 1 of the ALK gene, results from a G to T substitution at nucleotide position 175. The valine at codon 59 is replaced by leucine, 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. |