Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001210706 | SCV001382205 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1159 of the ALK protein (p.Gln1159Leu). 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: 941004). 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 | RCV002451458 | SCV002613956 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-27 | criteria provided, single submitter | clinical testing | The p.Q1159L variant (also known as c.3476A>T), located in coding exon 22 of the ALK gene, results from an A to T substitution at nucleotide position 3476. The glutamine at codon 1159 is replaced by leucine, an amino acid with dissimilar properties. This alteration was identified in the germline of 7/36,813 unselected Chinese individuals diagnosed with lung cancer that underwent paired somatic and germline testing (Yang J et al. Front Oncol, 2021 Apr;11:647598). This amino acid position is highly 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. |