Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001870906 | SCV002132204 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2021-07-14 | 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ALK-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 35 of the ALK protein (p.Gly35Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. |
| Baylor Genetics | RCV001870906 | SCV005058963 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-01-18 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001870906 | SCV005877652 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-09-13 | criteria provided, single submitter | clinical testing | The ALK c.103G>A; p.Gly35Arg variant, to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1369997). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Computational analyses predict that this variant is neutral (REVEL: 0.026). Due to limited information, the clinical significance of this variant is uncertain at this time. |
| Ambry Genetics | RCV005341105 | SCV006013353 | uncertain significance | Hereditary cancer-predisposing syndrome | 2025-01-08 | criteria provided, single submitter | clinical testing | The p.G35R variant (also known as c.103G>A), located in coding exon 1 of the ALK gene, results from a G to A substitution at nucleotide position 103. The glycine at codon 35 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |