Submissions for variant NM_017617.5(NOTCH1):c.851C>T (p.Pro284Leu)

gnomAD frequency: 0.00013  dbSNP: rs376104770

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000537829	SCV000659502	benign	Adams-Oliver syndrome 5	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002315062	SCV000739427	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2018-06-08	criteria provided, single submitter	clinical testing	The p.P284L variant (also known as c.851C>T), located in coding exon 5 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 851. The proline at codon 284 is replaced by leucine, an amino acid with similar properties. This alteration was detected in a proband and the proband's child with bicuspid aortic valve (Foffa I et al. BMC Med Genet. 2013;14:44). This variant was also detected in a patient with congenital heart disease as well as non-cardiac findings who also harbored other variants (Jin SC et al. Nat Genet. 2017;49(11):1593-1601). This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV001815410	SCV002063282	uncertain significance	not provided	2021-12-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000537829	SCV002553977	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270714	SCV002553978	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing