Submissions for variant NM_017617.5(NOTCH1):c.1775G>A (p.Arg592His)

gnomAD frequency: 0.00001  dbSNP: rs544117297

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002311177	SCV000320368	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2015-10-03	criteria provided, single submitter	clinical testing	The p.R592H variant (also known as c.1775G>A), located in coding exon 11 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 1775. The arginine at codon 592 is replaced by histidine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6463 samples (12926 alleles) with coverage at this position. This amino acid position is poorly 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 variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001854993	SCV002206577	benign	Adams-Oliver syndrome 5	2022-09-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001854993	SCV002553925	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270184	SCV002553926	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing