Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001050419 | SCV001214526 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-07-21 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 846976). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs774746810, gnomAD 0.003%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1518 of the ALK protein (p.Lys1518Asn). 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. 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. Experimental studies have shown that this missense change does not substantially affect ALK function (PMID: 22086496). |