Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001888055 | SCV002121832 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln1238Leufs*48) 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 not present in population databases (gnomAD no frequency). 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: 1355520). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | RCV004616798 | SCV005121144 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-21 | criteria provided, single submitter | clinical testing | The c.3709_3712dupTGTC variant, located in coding exon 24 of the ALK gene, results from a duplication of TGTC at nucleotide positions 3709 to 3712, causing a translational frameshift with a predicted alternate stop codon (p.Q1238Lfs*48). This alteration is expected to result in protein truncation or nonsense-mediated mRNA decay. However, loss of function of ALK has not been established as a mechanism of disease. Based on the available evidence, the clinical significance of this alteration remains unclear. |