Submissions for variant NM_017617.5(NOTCH1):c.541G>A (p.Glu181Lys)

gnomAD frequency: 0.00001  dbSNP: rs780209394

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001758209	SCV001985780	uncertain significance	not provided	2019-09-17	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV003120662	SCV003789419	likely benign	Adams-Oliver syndrome 5	2022-12-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV005382171	SCV006039510	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-12-28	criteria provided, single submitter	clinical testing	The p.E181K variant (also known as c.541G>A), located in coding exon 4 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 541. The glutamic acid at codon 181 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.