Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001058711 | SCV001223302 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1212 of the ALK protein (p.Arg1212Cys). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 853821). 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. 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 | RCV002460131 | SCV002618131 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-15 | criteria provided, single submitter | clinical testing | The p.R1212C variant (also known as c.3634C>T), located in coding exon 23 of the ALK gene, results from a C to T substitution at nucleotide position 3634. The arginine at codon 1212 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |