Submissions for variant NM_017617.5(NOTCH1):c.3860G>A (p.Arg1287His)

gnomAD frequency: 0.00003  dbSNP: rs763679772

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000680590	SCV000808015	likely benign	Connective tissue disorder	2018-06-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000690352	SCV000818034	likely benign	Adams-Oliver syndrome 5	2023-10-06	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000690352	SCV002554457	likely benign	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270961	SCV002554458	likely benign	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003432725	SCV004162029	uncertain significance	not provided	2022-07-01	criteria provided, single submitter	clinical testing	NOTCH1: PP2, BP4
Ambry Genetics	RCV004026160	SCV005027211	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-01-29	criteria provided, single submitter	clinical testing	The p.R1287H variant (also known as c.3860G>A), located in coding exon 23 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 3860. The arginine at codon 1287 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in a congenital heart disease cohort (Preuss C et al. PLoS Genet, 2016 Oct;12:e1006335). 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. Based on the available evidence, the clinical significance of this alteration remains unclear.