Submissions for variant NM_017617.5(NOTCH1):c.2705G>A (p.Arg902His)

dbSNP: rs373075482

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002315130	SCV000739498	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2022-11-27	criteria provided, single submitter	clinical testing	The p.R902H variant (also known as c.2705G>A), located in coding exon 17 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 2705. The arginine at codon 902 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in other 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 alteration remains unclear.
GeneDx	RCV001591392	SCV001823686	uncertain significance	not provided	2020-07-30	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 520086; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function
Invitae	RCV001855282	SCV002191916	likely benign	Adams-Oliver syndrome 5	2023-01-06	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001855282	SCV002553534	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270916	SCV002553535	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing