Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000791894 | SCV000931161 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp1295*) in the ALK gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ALK cause disease. This variant is present in population databases (no rsID available, 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: 639161). 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 | RCV002360909 | SCV002623889 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-20 | criteria provided, single submitter | clinical testing | The p.W1295* variant (also known as c.3884G>A), located in coding exon 26 of the ALK gene, results from a G to A substitution at nucleotide position 3884. This changes the amino acid from a tryptophan to a stop codon within coding exon 26. This alteration is expected to result in premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of ALK has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |