Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001348935 | SCV001543262 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2020-09-11 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ALK-related conditions. This variant is present in population databases (rs751170666, ExAC 0.001%). This sequence change replaces threonine with isoleucine at codon 1500 of the ALK protein (p.Thr1500Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
| Ambry Genetics | RCV003355416 | SCV004055742 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-29 | criteria provided, single submitter | clinical testing | The p.T1500I variant (also known as c.4499C>T), located in coding exon 29 of the ALK gene, results from a C to T substitution at nucleotide position 4499. The threonine at codon 1500 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |