Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000687955 | SCV000815550 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2022-09-10 | 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 567781). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs760038434, gnomAD 0.0009%). This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 614 of the ALK protein (p.Trp614Leu). |
Ambry Genetics | RCV003163118 | SCV003861069 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-08 | criteria provided, single submitter | clinical testing | The p.W614L variant (also known as c.1841G>T), located in coding exon 10 of the ALK gene, results from a G to T substitution at nucleotide position 1841. The tryptophan at codon 614 is replaced by leucine, 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. |