Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000647391 | SCV000769187 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 214 of the ALK protein (p.Arg214Cys). This variant is present in population databases (rs370297427, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 538189). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
Ambry Genetics | RCV002360610 | SCV002661211 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-09 | criteria provided, single submitter | clinical testing | The p.R214C variant (also known as c.640C>T), located in coding exon 1 of the ALK gene, results from a C to T substitution at nucleotide position 640. The arginine at codon 214 is replaced by cysteine, an amino acid with highly dissimilar 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. |
Gene |
RCV002461959 | SCV002756956 | uncertain significance | not provided | 2022-05-19 | 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 |
Baylor Genetics | RCV000647391 | SCV004190580 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-06-09 | criteria provided, single submitter | clinical testing |