Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001234147 | SCV001406777 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2020-03-07 | 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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 serine with phenylalanine at codon 1481 of the ALK protein (p.Ser1481Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. |
| Ambry Genetics | RCV002327563 | SCV002632604 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-05 | criteria provided, single submitter | clinical testing | The p.S1481F variant (also known as c.4442C>T), located in coding exon 29 of the ALK gene, results from a C to T substitution at nucleotide position 4442. The serine at codon 1481 is replaced by phenylalanine, an amino acid with highly dissimilar 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. |
| St. |
RCV001234147 | SCV004031249 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-07-26 | criteria provided, single submitter | clinical testing | The ALK c.4442C>T (p.Ser1481Phe) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with ALK-related neuroblastic tumor susceptibility. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
| Baylor Genetics | RCV001234147 | SCV004199895 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-08-09 | criteria provided, single submitter | clinical testing |