Submissions for variant NM_017617.5(NOTCH1):c.2434G>A (p.Gly812Arg)

gnomAD frequency: 0.00029  dbSNP: rs201620755

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Paul Sabatier University EA-4555, Paul Sabatier University	RCV000207430	SCV000259136	likely benign	Anophthalmia-microphthalmia syndrome	2013-01-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002315640	SCV000739406	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2020-08-20	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.
Invitae	RCV001450102	SCV001653699	likely benign	Adams-Oliver syndrome 5	2023-10-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000540543	SCV002098258	uncertain significance	not provided	2023-03-24	criteria provided, single submitter	clinical testing	Has not been previously published in association with NOTCH1-related cardiac disease or NOTCH1-related Adams Oliver syndrome to our knowledge; At the protein level, in silico analysis supports that this missense variant has a deleterious effect on protein structure/function; At the mRNA level, in silico analysis supports a deleterious effect on splicing; in the absence of RNA/functional studies, the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 26893459)
Revvity Omics, Revvity	RCV000540543	SCV003815984	uncertain significance	not provided	2021-03-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003917851	SCV004730317	likely benign	NOTCH1-related condition	2022-10-18	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).