Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002040685 | SCV002304426 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2021-05-09 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with ALK-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 1474 of the ALK protein (p.Gly1474Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |
Baylor Genetics | RCV002040685 | SCV004191162 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-05-12 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004046645 | SCV005021890 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-12 | criteria provided, single submitter | clinical testing | The p.G1474R variant (also known as c.4420G>C), located in coding exon 29 of the ALK gene, results from a G to C substitution at nucleotide position 4420. The glycine at codon 1474 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |