ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.952_953del (p.Glu318fs)

dbSNP: rs2066507116
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 RCV001070093 SCV001235304 pathogenic Neurofibromatosis, type 1 2024-01-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu318Lysfs*11) 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 clinical features of neurofibromatosis type 1 (PMID: 23913538). ClinVar contains an entry for this variant (Variation ID: 863185). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV002245852 SCV002513148 pathogenic not provided 2023-07-17 criteria provided, single submitter clinical testing Frameshift 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); This variant is associated with the following publications: (PMID: 31766501, 23913538)
Genome-Nilou Lab RCV001070093 SCV002561614 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002374994 SCV002686071 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-02-04 criteria provided, single submitter clinical testing The c.952_953delGA pathogenic mutation, located in coding exon 9 of the NF1 gene, results from a deletion of two nucleotides at nucleotide positions 952 to 953, causing a translational frameshift with a predicted alternate stop codon (p.E318Kfs*11). This alteration was found in 1/565 French patients with neurofibromatosis type 1 (Sabbagh A et al. Hum. Mutat., 2013 Nov;34:1510-8). 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.
Baylor Genetics RCV003469262 SCV004198998 pathogenic Juvenile myelomonocytic leukemia 2022-02-21 criteria provided, single submitter clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc RCV001070093 SCV005417428 pathogenic Neurofibromatosis, type 1 criteria provided, single submitter clinical testing PVS1+PM2_Supporting+PS4+PM6_Supporting

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.