ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.527G>A (p.Arg176Gln)

gnomAD frequency: 0.00009  dbSNP: rs375065108
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000466090 SCV000548947 benign Adams-Oliver syndrome 5 2024-07-24 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001508285 SCV001714339 uncertain significance not provided 2020-01-08 criteria provided, single submitter clinical testing
GeneDx RCV001508285 SCV001769707 uncertain significance not provided 2024-11-05 criteria provided, single submitter clinical testing Identified in a patient with bicuspid aortic valve in published literature (PMID: 35288444); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 35288444)
Genome-Nilou Lab RCV000466090 SCV002554001 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270502 SCV002554002 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002348312 SCV002643005 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-10-21 criteria provided, single submitter clinical testing The p.R176Q variant (also known as c.527G>A), located in coding exon 4 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 527. The arginine at codon 176 is replaced by glutamine, an amino acid with highly similar properties. This variant has been detected in a bicuspid aortic valve cohort; however, details were limited (Debiec RM et al. Heart, 2022 Mar [published online ahead of print], doi:10.1136/heartjnl-2021-320428). This amino acid position is not well conserved in available vertebrate species. 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.
John Welsh Cardiovascular Diagnostic Laboratory, Baylor College of Medicine RCV002285159 SCV002575043 likely benign Pulmonary arterial hypertension 2022-09-26 no assertion criteria provided clinical testing

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