Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000697086 | SCV000825676 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 704 of the ALK protein (p.Ala704Thr). This variant is present in population databases (rs34829159, gnomAD 0.006%). 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: 575004). 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 tolerated. 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. |
Gene |
RCV001771972 | SCV002002666 | uncertain significance | not provided | 2021-03-08 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function |
Prevention |
RCV003424290 | SCV004109798 | uncertain significance | ALK-related condition | 2022-09-06 | criteria provided, single submitter | clinical testing | The ALK c.2110G>A variant is predicted to result in the amino acid substitution p.Ala704Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-29474065-C-T) and is listed in ClinVar as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/575004/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Baylor Genetics | RCV000697086 | SCV004190513 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-06-16 | criteria provided, single submitter | clinical testing |