Submissions for variant NM_017617.5(NOTCH1):c.4238G>A (p.Arg1413His)

gnomAD frequency: 0.00005  dbSNP: rs371068504

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001798757	SCV000320436	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-06-16	criteria provided, single submitter	clinical testing	The p.R1413H variant (also known as c.4238G>A), located in coding exon 25 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 4238. The arginine at codon 1413 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Invitae	RCV000471799	SCV000548959	benign	Adams-Oliver syndrome 5	2023-12-21	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000766060	SCV000897516	uncertain significance	Aortic valve disease 1; Adams-Oliver syndrome 5	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001536590	SCV001753369	uncertain significance	not provided	2021-09-17	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign in association with NOTCH1-related disorders to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 264469; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 28682882)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798757	SCV002043521	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2020-04-09	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000471799	SCV002553432	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270187	SCV002553433	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001536590	SCV004162024	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	NOTCH1: PP2, BP4, BS1