ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3763C>T (p.Gln1255Ter)

dbSNP: rs1060500308
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000459390 SCV000542085 pathogenic Neurofibromatosis, type 1 2016-12-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1255 (p.Gln1255*) of the NF1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in NF1 are known to be pathogenic. This particular variant has been reported in the literature in an individual affected with neurofibromatosis type 1 (PMID: 23913538).
GeneDx RCV000522070 SCV000617581 pathogenic not provided 2017-04-05 criteria provided, single submitter clinical testing This variant is denoted NF1 c.3763C>T at the cDNA level and p.Gln1255Ter (Q1255X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least one individual with neurofibromatosis (Sabbagh 2013) and is considered pathogenic.
Genome-Nilou Lab RCV000459390 SCV002559986 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002348262 SCV002620366 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-01-27 criteria provided, single submitter clinical testing The p.Q1255* pathogenic mutation (also known as c.3763C>T), located in coding exon 28 of the NF1 gene, results from a C to T substitution at nucleotide position 3763. This changes the amino acid from a glutamine to a stop codon within coding exon 28. This mutation has been detected in individuals reported to have neurofibromatosis type 1 (Sabbagh A et al. Hum Mutat, 2013 Nov;34:1510-8; Kang E et al. J Hum Genet, 2020 Jan;65:79-89). 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.