Submissions for variant NM_017617.5(NOTCH1):c.701G>A (p.Arg234His)

gnomAD frequency: 0.00041  dbSNP: rs150737112

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000234727	SCV000290304	likely benign	Adams-Oliver syndrome 5	2024-01-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000121709	SCV000535035	likely benign	not specified	2018-02-02	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.
Ambry Genetics	RCV000769613	SCV000739362	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2021-03-02	criteria provided, single submitter	clinical testing	The c.701G>A (p.R234H) alteration is located in exon 4 (coding exon 4) of the NOTCH1 gene. This alteration results from a G to A substitution at nucleotide position 701, causing the arginine (R) at amino acid position 234 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000660139	SCV000782133	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769613	SCV000901010	benign	Familial thoracic aortic aneurysm and aortic dissection	2020-04-08	criteria provided, single submitter	clinical testing
ITMI	RCV000121709	SCV000085907	not provided	not specified	2013-09-19	no assertion provided	reference population
PreventionGenetics, part of Exact Sciences	RCV004542910	SCV004764787	likely benign	NOTCH1-related disorder	2022-06-29	no assertion criteria provided	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).