Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001362508 | SCV001558528 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2021-10-19 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This sequence change replaces glutamine with proline at codon 1429 of the ALK protein (p.Gln1429Pro). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ALK-related conditions. 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 | RCV002329364 | SCV002631785 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-29 | criteria provided, single submitter | clinical testing | The p.Q1429P variant (also known as c.4286A>C), located in coding exon 29 of the ALK gene, results from an A to C substitution at nucleotide position 4286. The glutamine at codon 1429 is replaced by proline, an amino acid with 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. |