Submissions for variant NM_017617.5(NOTCH1):c.1543G>C (p.Glu515Gln)

gnomAD frequency: 0.00003  dbSNP: rs749085650

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414177	SCV000492094	uncertain significance	not specified	2016-11-23	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the NOTCH1 gene. The E515Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E515Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved across species and where Glutamine is the wild type in several species. Finally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae	RCV001300961	SCV001490112	benign	Adams-Oliver syndrome 5	2023-12-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001300961	SCV002553948	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270242	SCV002553949	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing