ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.1250C>T (p.Ser417Leu)

gnomAD frequency: 0.00002  dbSNP: rs757631575
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000655265 SCV000777195 benign Adams-Oliver syndrome 5 2022-08-15 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001281020 SCV001468431 uncertain significance Aortic valve disease 1; Adams-Oliver syndrome 5 2021-03-30 criteria provided, single submitter clinical testing NOTCH1 NM_017617.4 esxon 7 p.Ser417Leu (c.1250C>T): This variant has not been reported in the literature but is present in 0.008% (9/106554) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-139412594-G-A). This variant is present in ClinVar (Variation ID:544189). Evolutionary conservation suggests that this variant may not impact the protein, but computational predicitve tools predict a deleterious effect. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx RCV001766427 SCV001998677 uncertain significance not provided 2020-01-10 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 544189; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Genome-Nilou Lab RCV000655265 SCV002553957 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270943 SCV002553958 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002406493 SCV002669064 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-05-30 criteria provided, single submitter clinical testing The p.S417L variant (also known as c.1250C>T), located in coding exon 7 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 1250. The serine at codon 417 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.