Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000707175 | SCV000836260 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2021-03-02 | criteria provided, single submitter | clinical testing | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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). This sequence change replaces lysine with arginine at codon 1416 of the ALK protein (p.Lys1416Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. |
| Ambry Genetics | RCV003372831 | SCV004073498 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-31 | criteria provided, single submitter | clinical testing | The p.K1416R variant (also known as c.4247A>G), located in coding exon 29 of the ALK gene, results from an A to G substitution at nucleotide position 4247. The lysine at codon 1416 is replaced by arginine, 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. |