ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4309_4311GAA[1] (p.Glu1438del) (rs267606607)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000544772 SCV000628588 likely pathogenic Neurofibromatosis, type 1 2018-11-25 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 32 of the NF1 mRNA (c.4312_4314delGAA). This leads to the deletion of 1 amino acid residue in the NF1 protein (p.Glu1438del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with classic neurofibromatosis type 1 (NF1) (PMID: 18546366, 15060124) and an individual with Neurofibromatosis-Noonan syndrome (NFNS) (PMID: 12707950). This variant also has been observed as de novo in an individual with multiple spinal ganglioneuromas and cafe-au-lait spots (PMID: 19863548). This variant is also known as 4312 del GAAdE1438 in the literature. ClinVar contain an entry for this variant (Variation ID: 364). This in-frame deletion is located in the GAP-related domain (GRD) of the NF1 protein (PMID: 24413922, 25877329). However, experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. In summary, this variant is a rare in-frame deletion with uncertain impact on protein function that has been reported in affected individuals including an individual with de novo observation. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000000394 SCV000020538 pathogenic Neurofibromatosis-Noonan syndrome 2003-05-15 no assertion criteria provided literature only

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.