Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000544098 | SCV000648722 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2017-01-30 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ALK-related disease. This sequence change replaces glycine with serine at codon 129 of the ALK protein (p.Gly129Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). |
Gene |
RCV003231645 | SCV003929921 | uncertain significance | not provided | 2022-12-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV003380620 | SCV004092510 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-01 | criteria provided, single submitter | clinical testing | The p.G129S variant (also known as c.385G>A), located in coding exon 1 of the ALK gene, results from a G to A substitution at nucleotide position 385. The glycine at codon 129 is replaced by serine, 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. |