Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001051460 | SCV001215615 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2025-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 993 of the ALK protein (p.Asp993Gly). This variant is not present in population databases (gnomAD no frequency). 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: 847831). 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 | RCV002436602 | SCV002751171 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-18 | criteria provided, single submitter | clinical testing | The p.D993G variant (also known as c.2978A>G), located in coding exon 18 of the ALK gene, results from an A to G substitution at nucleotide position 2978. The aspartic acid at codon 993 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV001051460 | SCV004198456 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-10-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004773264 | SCV005386662 | uncertain significance | not provided | 2024-01-17 | 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 |