Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000696428 | SCV000824990 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2019-07-11 | 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. ClinVar contains an entry for this variant (Variation ID: 574488). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 1316 of the ALK protein (p.Gly1316Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. |
Gene |
RCV002307597 | SCV002601250 | uncertain significance | not provided | 2022-05-06 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV003163202 | SCV003898022 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-12 | criteria provided, single submitter | clinical testing | The p.G1316E variant (also known as c.3947G>A), located in coding exon 27 of the ALK gene, results from a G to A substitution at nucleotide position 3947. The glycine at codon 1316 is replaced by glutamic acid, 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. |