Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000647478 | SCV000769274 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-03-31 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with ALK-related conditions. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 538269). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1097 of the ALK protein (p.Cys1097Arg). |
| Ambry Genetics | RCV002325282 | SCV002606016 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-07 | criteria provided, single submitter | clinical testing | The p.C1097R variant (also known as c.3289T>C), located in coding exon 20 of the ALK gene, results from a T to C substitution at nucleotide position 3289. The cysteine at codon 1097 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |