Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001051346 | SCV001215493 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-11-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1060 of the ALK protein (p.Arg1060His). This variant is present in population databases (rs769322016, gnomAD 0.02%). This missense change has been observed in individual(s) with neuroblastoma (PMID: 25517749). ClinVar contains an entry for this variant (Variation ID: 847740). 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. Experimental studies have shown that this missense change does not substantially affect ALK function (PMID: 25517749). 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. |
Gene |
RCV003442174 | SCV004169148 | uncertain significance | not provided | 2023-04-17 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies suggest no damaging effect: non-phosphorylated ALK kinase activity comparable to wild-type (Bresler et al., 2014); Observed in individuals with neuroblastoma (Bresler et al., 2014); This variant is associated with the following publications: (PMID: 25517749) |