Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001218163 | SCV001390035 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1216 of the ALK protein (p.Ser1216Gly). This variant is present in population databases (rs543229475, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 947154). 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 tolerated. 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. |
| Ambry Genetics | RCV002451492 | SCV002613825 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-29 | criteria provided, single submitter | clinical testing | The p.S1216G variant (also known as c.3646A>G) is located in coding exon 24 of the ALK gene. The serine at codon 1216 is replaced by glycine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 24. This amino acid position is not well conserved in available vertebrate species. 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. |