ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.4005G>A (p.Pro1335=)

gnomAD frequency: 0.00003  dbSNP: rs118188023
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000734920 SCV000863100 uncertain significance not provided 2018-08-28 criteria provided, single submitter clinical testing
Invitae RCV001868999 SCV002275532 uncertain significance Hajdu-Cheney syndrome 2024-01-15 criteria provided, single submitter clinical testing This sequence change affects codon 1335 of the NOTCH2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NOTCH2 protein. This variant also falls at the last nucleotide of exon 24, which is part of the consensus splice site for this exon. This variant is present in population databases (rs118188023, gnomAD 0.04%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with NOTCH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 598511). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
PreventionGenetics, part of Exact Sciences RCV003908058 SCV004732673 likely benign NOTCH2-related condition 2020-10-09 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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.