Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001227273 | SCV001399625 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-08-07 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs764207516, gnomAD 0.007%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 410 of the ALK protein (p.Gly410Arg). ClinVar contains an entry for this variant (Variation ID: 954757). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. |
Ambry Genetics | RCV003353225 | SCV004073531 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-08 | criteria provided, single submitter | clinical testing | The p.G410R variant (also known as c.1228G>A), located in coding exon 5 of the ALK gene, results from a G to A substitution at nucleotide position 1228. The glycine at codon 410 is replaced by arginine, an amino acid with dissimilar 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. |