Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
The Laboratory of Genetics and Metabolism, |
RCV001310089 | SCV001482304 | pathogenic | Alagille syndrome due to a NOTCH2 point mutation | 2019-07-26 | criteria provided, single submitter | clinical testing | First, the NOTCH2 variant p.(Met2042Thr) is a de novo variant in the patient with Alagille syndrome and no family history. Second, the variant is located in the ANK domain which was a mutational hot spot without benign variants. Third, this variant was absent from large population studies. Four, multiple lines of computational evidence support a deleterious effect on the gene NOTCH2. Five, this is a missense variant and NOTCH2 has a low rate of benign missense variation and where missense variants are a common mechanism of disease. |