Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000686482 | SCV000814001 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2022-09-21 | 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: 566619). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1043 of the ALK protein (p.Ala1043Val). |
| Ambry Genetics | RCV002325360 | SCV002607376 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-23 | criteria provided, single submitter | clinical testing | The p.A1043V variant (also known as c.3128C>T), located in coding exon 19 of the ALK gene, results from a C to T substitution at nucleotide position 3128. The alanine at codon 1043 is replaced by valine, 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. |