Submissions for variant NM_017617.5(NOTCH1):c.4373C>T (p.Ala1458Val)

gnomAD frequency: 0.00008  dbSNP: rs374352922

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001368999	SCV001565425	benign	Adams-Oliver syndrome 5	2024-01-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001751728	SCV001995513	uncertain significance	not provided	2019-12-02	criteria provided, single submitter	clinical testing	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
Genome-Nilou Lab	RCV001368999	SCV002553419	uncertain significance	Adams-Oliver syndrome 5	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002271234	SCV002553420	uncertain significance	Aortic valve disease 1	2022-03-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002493881	SCV002784731	uncertain significance	Aortic valve disease 1; Adams-Oliver syndrome 5	2021-10-29	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001751728	SCV003815993	uncertain significance	not provided	2019-07-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003169892	SCV003861087	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-01-17	criteria provided, single submitter	clinical testing	The p.A1458V variant (also known as c.4373C>T), located in coding exon 25 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 4373. The alanine at codon 1458 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate 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 alteration remains unclear.