Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000688109 | SCV000815709 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-06-28 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 567904). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs372008367, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 940 of the ALK protein (p.Gly940Cys). |
| Ambry Genetics | RCV001016674 | SCV001177654 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-06 | criteria provided, single submitter | clinical testing | The p.G940C variant (also known as c.2818G>T), located in coding exon 17 of the ALK gene, results from a G to T substitution at nucleotide position 2818. The glycine at codon 940 is replaced by cysteine, an amino acid with highly dissimilar 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. |