Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002375701 | SCV002625381 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-25 | criteria provided, single submitter | clinical testing | The p.K134Q variant (also known as c.400A>C), located in coding exon 1 of the ALK gene, results from an A to C substitution at nucleotide position 400. The lysine at codon 134 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Labcorp Genetics |
RCV003094481 | SCV003025561 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-03-23 | 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 1736990). This variant is present in population databases (rs775475622, gnomAD 0.001%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 134 of the ALK protein (p.Lys134Gln). |