ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.246_247del (p.Gln83fs)

dbSNP: rs771115661
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632345 SCV000753523 pathogenic Neurofibromatosis, type 1 2022-02-22 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Studies have shown that this premature translational stop signal alters NF1 gene expression (PMID: 25788518). ClinVar contains an entry for this variant (Variation ID: 527470). This variant is also known as c.240_241delTC. This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 16944272, 18546366, 23758643). This variant is present in population databases (rs771115661, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Gln83Valfs*23) 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).
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000632345 SCV000781867 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000632345 SCV002561561 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002458005 SCV002738204 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-04-21 criteria provided, single submitter clinical testing The c.246_247delTC pathogenic mutation, located in coding exon 3 of the NF1 gene, results from a deletion of two nucleotides at nucleotide positions 246 to 247, causing a translational frameshift with a predicted alternate stop codon (p.Q83Vfs*23). This alteration was identified in two separate cohorts undergoing genetic testing due to a diagnosis or clinical suspicion of neurofibromatosis type 1 (Pros E et al. Hum Mutat, 2008 Sep;29:E173-93; Bolcekova A et al. Neoplasma, 2013;60:655-65). 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.

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.