ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4606dup (p.Thr1536fs) (rs1555619033)

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
GeneDx RCV000599245 SCV000710063 pathogenic not provided 2017-11-14 criteria provided, single submitter clinical testing The c.4606dupA variant in the NF1 gene has been reported previously in association with NF1 (Bianchessi et al., 2015). The duplication causes a frameshift starting with codon Threonine 1536, changes this amino acid to an Asparagine residue and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Thr1536AsnfsX7. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be pathogenic.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000660062 SCV000782030 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022772 SCV001184546 pathogenic Hereditary cancer-predisposing syndrome 2018-01-03 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000660062 SCV001224846 pathogenic Neurofibromatosis, type 1 2019-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr1536Asnfs*7) in the NF1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with neurofibromatosis type 1 (PMID: 26740943). ClinVar contains an entry for this variant (Variation ID: 503769). Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as 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.