ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1185+1G>A

dbSNP: rs864622161
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204498 SCV000259511 pathogenic Neurofibromatosis, type 1 2021-10-20 criteria provided, single submitter clinical testing This variant is also known as IVS8+1G>A. Disruption of this splice site has been observed in individuals with neurofibromatosis type I (PMID: 10607834, 16835897, 18546366). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 10 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). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the c.1185+1G nucleotide in the NF1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 8957181, 11726231). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 219572).
Medical Genetics, University of Parma RCV000204498 SCV001218912 pathogenic Neurofibromatosis, type 1 2019-12-20 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001091254 SCV001247181 pathogenic not provided 2018-12-01 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000204498 SCV001479018 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000204498 SCV002561637 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000204498 SCV002579185 pathogenic Neurofibromatosis, type 1 2022-04-19 criteria provided, single submitter clinical testing
GeneDx RCV001091254 SCV003918478 pathogenic not provided 2023-04-03 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in an in-frame deletion of exon 10, confirmed by mRNA analysis in patient cells (Ars et al., 2000, Anastasaki et al., 2015, Giugliano et al., 2019); Deletions involving coding exons in this gene are frequently reported as pathogenic, regardless of frame prediction (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); A different pathogenic splice variant at this residue (c.1185+1 G>T) has been reported as pathogenic in the published literature in association with NF1-related neurofibromatosis (Horn et al., 1996); Also known as IVS8+1G>A; This variant is associated with the following publications: (PMID: 8957181, 25788518, 34427956, 25525159, 17726231, 10607834, 24361808, 16835897, 18546366, 32243842, 31370276)
Baylor Genetics RCV003462367 SCV004198382 pathogenic Juvenile myelomonocytic leukemia 2023-08-04 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.