Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000647423 | SCV000769219 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 231 of the ALK protein (p.Thr231Arg). This variant is present in population databases (rs142120301, gnomAD 0.03%). 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: 538218). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Sema4, |
RCV002256446 | SCV002528535 | likely benign | Hereditary cancer-predisposing syndrome | 2021-10-19 | criteria provided, single submitter | curation | |
| Ambry Genetics | RCV002256446 | SCV002668220 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-12 | criteria provided, single submitter | clinical testing | The p.T231R variant (also known as c.692C>G), located in coding exon 2 of the ALK gene, results from a C to G substitution at nucleotide position 692. The threonine at codon 231 is replaced by arginine, 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. |
| Gene |
RCV003317320 | SCV004021902 | uncertain significance | not provided | 2023-01-19 | criteria provided, single submitter | clinical testing | 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; This variant is associated with the following publications: (PMID: 25054154) |
| Baylor Genetics | RCV000647423 | SCV005059851 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-11-21 | criteria provided, single submitter | clinical testing |