Submissions for variant NM_017617.5(NOTCH1):c.3271G>A (p.Gly1091Ser)

gnomAD frequency: 0.00006  dbSNP: rs768095251

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000233859	SCV000290264	likely benign	Adams-Oliver syndrome 5	2025-01-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001589195	SCV001826179	uncertain significance	not provided	2023-12-21	criteria provided, single submitter	clinical testing	Reported in an Australian female with an atrial septal defect (ASD), whose mother and maternal grandmother also had an ASD (PMID: 25500235); however, while the p.(G1091S) variant was found in her affected mother, it was not detected in her affected maternal grandmother; Also reported in two Dutch individuals, one individual with a bicuspid aortic valve and one individual with hypoplastic left heart syndrome, and both individuals inherited the variant from their mothers who had normal echocardiograms (PMID: 26820064); 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: 25803323, 24030381, 29217782, 26820064, 25500235)
Genome-Nilou Lab	RCV000233859	SCV002553503	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270042	SCV002553505	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002444917	SCV002612547	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-09-26	criteria provided, single submitter	clinical testing	The c.3271G>A (p.G1091S) alteration is located in exon 20 (coding exon 20) of the NOTCH1 gene. This alteration results from a G to A substitution at nucleotide position 3271, causing the glycine (G) at amino acid position 1091 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV001589195	SCV005197002	uncertain significance	not provided	2023-03-22	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001589195	SCV001928815	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001589195	SCV001956845	uncertain significance	not provided		no assertion criteria provided	clinical testing