Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001049458 | SCV001213507 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-02-15 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1378 of the ALK protein (p.Ile1378Val). This variant is not present in population databases (gnomAD no frequency). 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: 846209). 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 | RCV002327297 | SCV002628846 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-19 | criteria provided, single submitter | clinical testing | The p.I1378V variant (also known as c.4132A>G), located in coding exon 28 of the ALK gene, results from an A to G substitution at nucleotide position 4132. The isoleucine at codon 1378 is replaced by valine, an amino acid with highly similar properties. 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. |