ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5521C>T (p.Gln1841Ter)

dbSNP: rs786203570
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000206167 SCV000260771 pathogenic Neurofibromatosis, type 1 2023-05-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1820*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with neurofibromatosis 1 (PMID: 10090487). ClinVar contains an entry for this variant (Variation ID: 220317). For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000206167 SCV001479016 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
GeneDx RCV001824299 SCV002073984 pathogenic not provided 2024-04-02 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); Also known as c.5458C>T; p.Gln1828X; This variant is associated with the following publications: (PMID: 23404336, 10712197, 25525159, 10090487, 23913538, 22190595, 31573083)
Genome-Nilou Lab RCV000206167 SCV002560127 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002345737 SCV002649721 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-05-20 criteria provided, single submitter clinical testing The p.Q1820* pathogenic mutation (also known as c.5458C>T), located in coding exon 37 of the NF1 gene, results from a C to T substitution at nucleotide position 5458. This changes the amino acid from a glutamine to a stop codon within coding exon 37. This alteration has been reported in individuals meeting diagnostic criteria for neurofibromatosis type 1 (NF1) or with NF1 features (Peters H et al. Hum. Mutat., 1999;13:258; Ribeiro MJ et al. Invest Ophthalmol Vis Sci, 2012 Jan;53:287-93; Violante IR et al. Brain, 2013 Mar;136:918-25; Castellanos E et al. Clin Genet, 2020 02;97:264-275). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas RCV000206167 SCV004101045 likely pathogenic Neurofibromatosis, type 1 2023-11-02 no assertion criteria provided 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.