ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.7498C>G (p.His2500Asp)

gnomAD frequency: 0.00004  dbSNP: rs763902589
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000576306 SCV000678229 uncertain significance Aortic valve disease 1; Adams-Oliver syndrome 5 2021-03-30 criteria provided, single submitter clinical testing NOTCH1 NM_017617.4 exon34 p.His2500Asp (c.7498C>G): This variant has not been reported in the literature but is present in 9/121248 European chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs763902589). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae RCV001859994 SCV002124851 benign Adams-Oliver syndrome 5 2024-01-08 criteria provided, single submitter clinical testing
GeneDx RCV002259354 SCV002538820 uncertain significance not provided 2022-06-08 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Genome-Nilou Lab RCV001859994 SCV002555193 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270715 SCV002555194 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002395498 SCV002669826 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-11-07 criteria provided, single submitter clinical testing The p.H2500D variant (also known as c.7498C>G), located in coding exon 34 of the NOTCH1 gene, results from a C to G substitution at nucleotide position 7498. The histidine at codon 2500 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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