ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1660C>T (p.Gln554Ter)

dbSNP: rs953440640
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659999 SCV000781926 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756430 SCV000884248 pathogenic not provided 2017-06-07 criteria provided, single submitter clinical testing The NF1 c.1660C>T;p.Gln554Ter variant is listed as pathogenic in a gene-specific database in two individuals (see link below). Additionally, according to a personal communication with the Human Gene Mutation Database, this variant was also included in van Minkelen 2014. The variant is not listed in the ClinVar database, the dbSNP variant database, or in the general population-based databases (Exome Variant Server, Genome Aggregation Database). This variant introduces a premature termination codon and is predicted to result in a truncated or absent protein. Considering available information, this variant is classified as pathogenic. References: Link to NF1 database: https://grenada.lumc.nl/LOVD2/mendelian_genes/home.php?select_db=NF1 van Minkelen R et al. A clinical and genetic overview of 18 years neurofibromatosis type 1 molecular diagnostics in the Netherlands. Clin Genet. 2014 Apr;85(4):318-27.
Invitae RCV000659999 SCV002243801 pathogenic Neurofibromatosis, type 1 2021-10-09 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 547601). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln554*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538).
Genome-Nilou Lab RCV000659999 SCV002561689 likely pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000659999 SCV002580418 pathogenic Neurofibromatosis, type 1 2021-10-04 criteria provided, single submitter clinical testing
GeneDx RCV000756430 SCV004169797 pathogenic not provided 2023-05-10 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in a patient in the published literature; however, this patient's phenotype was not described (Cho et al., 2017); This variant is associated with the following publications: (PMID: 23656349, 28851938)

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.