ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.2440A>G (p.Ile814Val)

gnomAD frequency: 0.00001  dbSNP: rs782757612
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001903354 SCV002162297 uncertain significance Hajdu-Cheney syndrome 2021-04-02 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NOTCH2 protein function. This variant has not been reported in the literature in individuals with NOTCH2-related conditions. This variant is present in population databases (rs782757612, ExAC 0.001%). This sequence change replaces isoleucine with valine at codon 814 of the NOTCH2 protein (p.Ile814Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine.
MGZ Medical Genetics Center RCV002290792 SCV002579958 uncertain significance Alagille syndrome due to a NOTCH2 point mutation 2022-05-18 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.