Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000793122 | SCV000932462 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2022-12-18 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 640156). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs752568687, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 929 of the ALK protein (p.Ser929Phe). |
Sema4, |
RCV002257955 | SCV002528440 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-31 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002257955 | SCV002751715 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-27 | criteria provided, single submitter | clinical testing | The p.S929F variant (also known as c.2786C>T), located in coding exon 16 of the ALK gene, results from a C to T substitution at nucleotide position 2786. The serine at codon 929 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. |