Submissions for variant NM_017617.5(NOTCH1):c.3001G>A (p.Gly1001Ser)

gnomAD frequency: 0.00006  dbSNP: rs763621169

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002315122	SCV000739490	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-04-29	criteria provided, single submitter	clinical testing	The p.G1001S variant (also known as c.3001G>A), located in coding exon 19 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 3001. The glycine at codon 1001 is replaced by serine, an amino acid with similar properties. This alteration has been reported in a thoracic aortic aneurysm and dissection (TAAD) cohort and an ischemic stroke cohort (Overwater E et al. Hum Mutat, 2018 Sep;39:1173-1192; Alkhamis FA et al. Funct Integr Genomics, 2023 Mar;23:102). This amino acid position is highly conserved in available vertebrate species. 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000796996	SCV000936533	likely benign	Adams-Oliver syndrome 5	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001557407	SCV001779163	uncertain significance	not provided	2023-11-09	criteria provided, single submitter	clinical testing	Reported as a variant of uncertain significance in an individual with thoracic aortic aneurysm (PMID: 29907982); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29907982)
Genome-Nilou Lab	RCV000796996	SCV002553517	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270910	SCV002553518	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483734	SCV002801387	uncertain significance	Aortic valve disease 1; Adams-Oliver syndrome 5	2022-02-22	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001557407	SCV001798756	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001557407	SCV001808847	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001557407	SCV001974764	uncertain significance	not provided		no assertion criteria provided	clinical testing