Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000201876 | SCV000769176 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-07-25 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1229 of the ALK protein (p.Val1229Met). This variant is present in population databases (rs776228721, gnomAD 0.01%). 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: 217853). 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 | RCV002453730 | SCV002613710 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-16 | criteria provided, single submitter | clinical testing | The p.V1229M variant (also known as c.3685G>A), located in coding exon 24 of the ALK gene, results from a G to A substitution at nucleotide position 3685. The valine at codon 1229 is replaced by methionine, an amino acid with highly similar properties. This variant has been reported in 1/1120 pediatric cancer patients who underwent whole genome sequencing and/or whole exome sequencing; this patient was diagnosed with acute lymphoblastic leukemia (ALL) (Zhang J et al. N Engl J Med, 2015 Dec;373:2336-2346). This amino acid position is well conserved in available vertebrate species. 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. |
| Genomic Diagnostic Laboratory, |
RCV000201876 | SCV000256819 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2015-10-07 | no assertion criteria provided | clinical testing |