Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000461079 | SCV000541893 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2016-10-25 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ALK-related disease. This sequence change replaces isoleucine with valine at codon 1088 of the ALK protein (p.Ile1088Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. |
| Ambry Genetics | RCV003298467 | SCV004006573 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-05 | criteria provided, single submitter | clinical testing | The p.I1088V variant (also known as c.3262A>G), located in coding exon 20 of the ALK gene, results from an A to G substitution at nucleotide position 3262. The isoleucine at codon 1088 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |