Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000460983 | SCV000541876 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 367 of the ALK protein (p.Pro367Arg). This variant is present in population databases (rs144030155, gnomAD 0.03%). 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: 133482). 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. |
St. |
RCV000460983 | SCV002526059 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-05-23 | criteria provided, single submitter | clinical testing | The ALK c.1100C>G (p.Pro367Arg) missense change has a maximum subpopulation frequency of 0.022% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with ALK-related neuroblastic tumor susceptibility. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Sema4, |
RCV002256051 | SCV002528377 | likely benign | Hereditary cancer-predisposing syndrome | 2021-06-13 | criteria provided, single submitter | curation | |
Gene |
RCV003223611 | SCV003919606 | likely benign | not provided | 2023-04-18 | criteria provided, single submitter | clinical testing | See Variant Classification Assertion Criteria. |
ITMI | RCV000119986 | SCV000084116 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |