Submissions for variant NM_017617.5(NOTCH1):c.7016C>A (p.Ala2339Asp)

gnomAD frequency: 0.00005  dbSNP: rs773134608

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001048112	SCV001212101	benign	Adams-Oliver syndrome 5	2023-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001776105	SCV002013432	uncertain significance	not provided	2024-01-30	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001799033	SCV002043542	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2020-07-23	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001048112	SCV002553266	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002271173	SCV002553267	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001799033	SCV002666898	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-02-25	criteria provided, single submitter	clinical testing	The p.A2339D variant (also known as c.7016C>A), located in coding exon 34 of the NOTCH1 gene, results from a C to A substitution at nucleotide position 7016. The alanine at codon 2339 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.