Submissions for variant NM_017617.5(NOTCH1):c.581C>T (p.Thr194Ile)

gnomAD frequency: 0.00001  dbSNP: rs760005580

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001037840	SCV001201272	benign	Adams-Oliver syndrome 5	2023-05-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001759730	SCV001986401	uncertain significance	not provided	2019-08-08	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Genome-Nilou Lab	RCV001037840	SCV002553999	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002271168	SCV002554000	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002354983	SCV002648281	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2019-07-10	criteria provided, single submitter	clinical testing	The p.T194I variant (also known as c.581C>T), located in coding exon 4 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 581. The threonine at codon 194 is replaced by isoleucine, an amino acid with 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV002354983	SCV004239535	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2022-11-08	criteria provided, single submitter	clinical testing