Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000559323 | SCV000648729 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change affects codon 1326 of the ALK mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ALK protein. This variant is present in population databases (rs200256900, gnomAD 0.003%). 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: 470860). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 | RCV002324014 | SCV002626366 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-12 | criteria provided, single submitter | clinical testing | The c.3978A>G variant (also known as p.G1326G) is located in coding exon 27 of the ALK gene. This variant results from an A to G substitution at nucleotide position 3978. This nucleotide substitution does not change the gylcine at codon 1326. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |