Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001967304 | SCV002202770 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2020-12-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with aspartic acid at codon 718 of the ALK protein (p.Gly718Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ALK-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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV004041908 | SCV005021456 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-29 | criteria provided, single submitter | clinical testing | The p.G718D variant (also known as c.2153G>A), located in coding exon 12 of the ALK gene, results from a G to A substitution at nucleotide position 2153. The glycine at codon 718 is replaced by aspartic acid, an amino acid with 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. |