Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001212607 | SCV001384196 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2022-10-06 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 18 of the ALK protein (p.Ala18Pro). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 942592). |
| Ambry Genetics | RCV003163613 | SCV003859057 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-25 | criteria provided, single submitter | clinical testing | The p.A18P variant (also known as c.52G>C), located in coding exon 1 of the ALK gene, results from a G to C substitution at nucleotide position 52. The alanine at codon 18 is replaced by proline, 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. |