Submissions for variant NM_017617.5(NOTCH1):c.433G>A (p.Ala145Thr)

dbSNP: rs1388726872

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001343127	SCV001537091	benign	Adams-Oliver syndrome 5	2022-12-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001751670	SCV001988026	uncertain significance	not provided	2021-04-29	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 1039617; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function
Genome-Nilou Lab	RCV001343127	SCV002554012	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002271223	SCV002554013	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002329320	SCV002630972	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2021-10-13	criteria provided, single submitter	clinical testing	The p.A145T variant (also known as c.433G>A), located in coding exon 4 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 433. The alanine at codon 145 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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.
Department of Human Genetics, Nagasaki University	RCV003159076	SCV003762185	other	Cholesteatoma of middle ear		criteria provided, single submitter	research	variant allele frequency in tumor is 0.0681 (54/739)