Submissions for variant NM_017617.5(NOTCH1):c.5690C>T (p.Thr1897Met)

gnomAD frequency: 0.00001  dbSNP: rs746237272

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002310923	SCV000319509	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2015-03-26	criteria provided, single submitter	clinical testing	The p.T1897M variant (also known as c.5690C>T), located in coding exon 31 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 5690. The threonine at codon 1897 is replaced by methionine, an amino acid with some similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6245 samples (12490 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrates, however methionine is the reference amino acid in one species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000687731	SCV000815316	benign	Adams-Oliver syndrome 5	2023-09-23	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000687731	SCV002553329	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002270157	SCV002553330	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing