Submissions for variant NM_017617.5(NOTCH1):c.3282C>A (p.Cys1094Ter)

dbSNP: rs748813647

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology	RCV003326287	SCV004032426	likely pathogenic	Aortic valve disease 1	2023-05-05	criteria provided, single submitter	clinical testing	A heterozygous variant in the NOTCH1 gene (9-136508275-G-T) resulting in a premature translation termination site (p.Cys1094Ter, NM_017617) has been identified. Heterozygous variants in the NOTCH1 gene have been described in patients with aortic valve disease and Adams-Oliver syndrome (OMIM: 109730, 616028). Not reported in gnomAD. Based on the totality of the evidence, the variant should be considered as likely pathogenic.
Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology	RCV003985881	SCV004801872	likely pathogenic	Aortic valve disease 1; Adams-Oliver syndrome 5		criteria provided, single submitter	clinical testing	A previously undescribed nucleotide variant creates a premature translation stop signal p.Cys1094Ter in the NOTCH1 gene. The variant was observed in heterozygous state in an individual affected with congenital heart defect including double-outlet right ventrical and right aortic arch. Loss-of-function variants are reported in patients with Adams-Oliver syndrome 5, 616028, Aortic valve disease 1, 109730. The variant is not present in population database (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as likely pathogenic.