Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000799521 | SCV000939186 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2018-11-05 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ALK-related disease. This sequence change replaces tyrosine with histidine at codon 984 of the ALK protein (p.Tyr984His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. |
| Ambry Genetics | RCV002440666 | SCV002751945 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-20 | criteria provided, single submitter | clinical testing | The p.Y984H variant (also known as c.2950T>C), located in coding exon 18 of the ALK gene, results from a T to C substitution at nucleotide position 2950. The tyrosine at codon 984 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. 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. |