Submissions for variant NM_017617.5(NOTCH1):c.4793G>A (p.Arg1598His)

gnomAD frequency: 0.00005  dbSNP: rs755124691

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002315097	SCV000739443	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-08-16	criteria provided, single submitter	clinical testing	The p.R1598H variant (also known as c.4793G>A), located in coding exon 26 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 4793. The arginine at codon 1598 is replaced by histidine, an amino acid with highly similar properties. 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 variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000655234	SCV000777164	benign	Adams-Oliver syndrome 5	2025-01-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001653955	SCV001871197	uncertain significance	not provided	2024-05-23	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign in association with NOTCH1-related disorders to our knowledge
Genome-Nilou Lab	RCV000655234	SCV002553392	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270890	SCV002553394	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001653955	SCV003815981	uncertain significance	not provided	2021-12-21	criteria provided, single submitter	clinical testing