Submissions for variant NM_001042492.3(NF1):c.889-1G>A

dbSNP: rs587781517

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000497206	SCV000781882	likely pathogenic	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000497206	SCV001207588	pathogenic	Neurofibromatosis, type 1	2023-08-08	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 431574). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individuals with clinical diagnosis or suspicion of neurofibromatosis type 1 (PMID: 10076878, 18546366, 24789688, 30308447). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 8 of the NF1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538).
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000497206	SCV001479005	pathogenic	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000497206	SCV002561611	likely pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Medical Genetics, University of Parma	RCV000497206	SCV000588708	likely pathogenic	Neurofibromatosis, type 1	2017-02-02	no assertion criteria provided	clinical testing