ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.587-14T>A

dbSNP: rs940581106
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UAB Medical Genomics Laboratory, UAB Medicine RCV001007709 SCV001167381 pathogenic Neurofibromatosis, type 1 2020-01-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001007709 SCV002316601 uncertain significance Neurofibromatosis, type 1 2021-11-23 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 23913538, 32126153). ClinVar contains an entry for this variant (Variation ID: 816723). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004559833 SCV005048399 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-03-05 criteria provided, single submitter clinical testing The c.587-14T>A intronic variant results from a T to A substitution 14 nucleotides upstream from coding exon 6 in the NF1 gene. This variant was identified in 1 of 565 unrelated French probands with clinical diagnoses or suspicion of NF1, and RT-PCR from blood leukocytes followed by cDNA sequencing showed this variant to result in loss of the acceptor splice site leading to skipping of exon 4c (Sabbagh A et al. Hum Mutat, 2013 Nov;34:1510-8). Another study, using direct cDNA sequencing of NF1 transcripts isolated from puromycin treated short term lymphocyte culture, demonstrated skipping of exon 6 (also known as exon 4c) leading to a frameshift (Wimmer K et al. Hum Mutat, 2020 Jun;41:1145-1156). This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice acceptor site. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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.