Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002366251 | SCV002624236 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-16 | criteria provided, single submitter | clinical testing | The p.M1290T variant (also known as c.3869T>C), located in coding exon 26 of the ALK gene, results from a T to C substitution at nucleotide position 3869. The methionine at codon 1290 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly 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. |
Labcorp Genetics |
RCV003094409 | SCV003459384 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2022-07-09 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1290 of the ALK protein (p.Met1290Thr). |