Submissions for variant NM_017617.5(NOTCH1):c.2354-5T>C

gnomAD frequency: 0.00014  dbSNP: rs371944522

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001721400	SCV000532746	likely benign	not provided	2021-05-24	criteria provided, single submitter	clinical testing
Invitae	RCV000475073	SCV000559888	likely benign	Adams-Oliver syndrome 5	2024-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002313123	SCV000739453	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2019-12-19	criteria provided, single submitter	clinical testing	The c.2354-5T>C intronic variant results from a T to C substitution 5 nucleotides upstream from coding exon 15 in the NOTCH1 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor/donor site; however, direct evidence is unavailable. 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	RCV002313123	SCV003838468	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2021-06-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003323538	SCV004029543	benign	not specified	2023-07-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925287	SCV004745455	likely benign	NOTCH1-related condition	2019-09-11	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).