Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003002790 | SCV003298677 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2022-10-08 | 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1434 of the ALK protein (p.Glu1434Gly). |
Baylor Genetics | RCV003002790 | SCV005058878 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-02-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004632144 | SCV005121165 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-09 | criteria provided, single submitter | clinical testing | The p.E1434G variant (also known as c.4301A>G), located in coding exon 29 of the ALK gene, results from an A to G substitution at nucleotide position 4301. The glutamic acid at codon 1434 is replaced by glycine, 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. Based on the available evidence, the clinical significance of this variant remains unclear. |