Submissions for variant NM_017617.5(NOTCH1):c.674C>G (p.Ser225Trp)

gnomAD frequency: 0.00001  dbSNP: rs553542677

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000815491	SCV000955949	benign	Adams-Oliver syndrome 5	2022-12-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001545874	SCV001765287	uncertain significance	not provided	2022-04-05	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
AiLife Diagnostics, AiLife Diagnostics	RCV001545874	SCV002503088	uncertain significance	not provided	2021-12-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000815491	SCV002553992	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002271047	SCV002553993	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002372300	SCV002667379	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-05-12	criteria provided, single submitter	clinical testing	The p.S225W variant (also known as c.674C>G), located in coding exon 4 of the NOTCH1 gene, results from a C to G substitution at nucleotide position 674. The serine at codon 225 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.