ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.35C>T (p.Ala12Val)

dbSNP: rs1473062369
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001765924 SCV002000606 uncertain significance not provided 2021-04-16 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001868647 SCV002189970 uncertain significance Adams-Oliver syndrome 5 2022-05-25 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1314883). 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 NOTCH1 protein function. 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. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 12 of the NOTCH1 protein (p.Ala12Val).
Genome-Nilou Lab RCV001868647 SCV002554027 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002271297 SCV002554028 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002458593 SCV002617383 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-03-23 criteria provided, single submitter clinical testing The p.A12V variant (also known as c.35C>T), located in coding exon 1 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 35. The alanine at codon 12 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002503231 SCV002775901 uncertain significance Aortic valve disease 1; Adams-Oliver syndrome 5 2021-07-26 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.