Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000545962 | SCV000648639 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2019-07-12 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 disruptive, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs755124993, ExAC 0.009%) but has not been reported in the literature in individuals with an ALK-related disease. This sequence change replaces asparagine with lysine at codon 654 of the ALK protein (p.Asn654Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. |
Ambry Genetics | RCV002420485 | SCV002722160 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-09 | criteria provided, single submitter | clinical testing | The p.N654K variant (also known as c.1962C>A), located in coding exon 11 of the ALK gene, results from a C to A substitution at nucleotide position 1962. The asparagine at codon 654 is replaced by lysine, 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. |