Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001063831 | SCV001228694 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-03-30 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1259 of the ALK protein (p.Cys1259Tyr). 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 858036). |
| Ambry Genetics | RCV002348456 | SCV002623508 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-06-26 | criteria provided, single submitter | clinical testing | The p.C1259Y variant (also known as c.3776G>A), located in coding exon 25 of the ALK gene, results from a G to A substitution at nucleotide position 3776. The cysteine at codon 1259 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is well 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. |