Submissions for variant NM_017617.5(NOTCH1):c.3528C>T (p.His1176=)

gnomAD frequency: 0.00020  dbSNP: rs202133782

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726368	SCV000344123	uncertain significance	not provided	2016-08-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000260648	SCV000530503	likely benign	not specified	2016-10-20	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000539966	SCV000659425	benign	Adams-Oliver syndrome 5	2024-01-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001171110	SCV000739431	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-12-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001171110	SCV001333789	benign	Familial thoracic aortic aneurysm and aortic dissection	2019-03-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000726368	SCV004564139	benign	not provided	2023-03-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003940072	SCV004749099	likely benign	NOTCH1-related condition	2019-06-03	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).