Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000811560 | SCV000951832 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2020-06-10 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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, 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 variant is present in population databases (rs759144859, ExAC 0.009%). This sequence change replaces glycine with serine at codon 1261 of the ALK protein (p.Gly1261Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. |
| Ambry Genetics | RCV004028733 | SCV005021967 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-29 | criteria provided, single submitter | clinical testing | The p.G1261S variant (also known as c.3781G>A), located in coding exon 25 of the ALK gene, results from a G to A substitution at nucleotide position 3781. The glycine at codon 1261 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |