Submissions for variant NM_017617.5(NOTCH1):c.157G>A (p.Val53Met)

gnomAD frequency: 0.00001  dbSNP: rs757497167

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000477441	SCV000548934	benign	Adams-Oliver syndrome 5	2023-12-20	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170716	SCV001333317	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2019-03-21	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000477441	SCV002554023	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270499	SCV002554024	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001170716	SCV002704157	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2020-07-31	criteria provided, single submitter	clinical testing	The p.V53M variant (also known as c.157G>A), located in coding exon 3 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 157. The valine at codon 53 is replaced by methionine, an amino acid with highly similar properties. This variant was detected in an individual with bicuspid aortic valve and thoracic aortic aneurysm and the affected father; however, clinical details were limited (Proost D et al. Hum. Mutat., 2015 Aug;36:808-14). 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.
Revvity Omics, Revvity	RCV003133272	SCV003815985	uncertain significance	not provided	2022-07-18	criteria provided, single submitter	clinical testing