Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570452 | SCV000672487 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-02 | criteria provided, single submitter | clinical testing | The p.E1340G variant (also known as c.4019A>G), located in coding exon 27 of the ALK gene, results from an A to G substitution at nucleotide position 4019. The glutamic acid at codon 1340 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000819572 | SCV000960239 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2018-07-10 | criteria provided, single submitter | clinical testing | 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 C0"). This variant has not been reported in the literature in individuals with ALK-related disease. ClinVar contains an entry for this variant (Variation ID: 485086). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 1340 of the ALK protein (p.Glu1340Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. 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. |