Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics Munich, |
RCV000995868 | SCV001150252 | pathogenic | Intellectual disability, autosomal dominant 29 | 2019-06-07 | criteria provided, single submitter | clinical testing | |
Principal Investigator Group 2, |
RCV000995868 | SCV005442721 | likely pathogenic | Intellectual disability, autosomal dominant 29 | no assertion criteria provided | clinical testing | This variant results in the 809th amino acid in SKI domain replaced by a stop codon and causes termination of the SETBP1 protein. The SETBP1 gene is of sufficient evidence for dosage pathogenicity and was absent from large population studies. This variant has been reported with Autosomal dominant inheritance (VCV000807682.2) C, and we confirmed it in a Chinese family. Additionally, the SETBP1 knock out by CRISPR/Cas9 affects forebrain progenitor expansion and neurogenic differentiation in hESC lines. In summary, the Gln809* variant meet our criteria to be classified as pathogenic (www.partners.org/personalizedmedicine/lmm) based upon segregation studies, absence from controls, and functional evidence. |