ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1139T>C (p.Leu380Pro)

dbSNP: rs1555611004
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
Invitae RCV000534870 SCV000628347 pathogenic Neurofibromatosis, type 1 2023-04-28 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 380 of the NF1 protein (p.Leu380Pro). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 457516). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 21520333, 27999334; Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics RCV002456060 SCV002614278 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-02-23 criteria provided, single submitter clinical testing The p.L380P variant (also known as c.1139T>C), located in coding exon 10 of the NF1 gene, results from a T to C substitution at nucleotide position 1139. The leucine at codon 380 is replaced by proline, an amino acid with similar properties. This variant has been detected in multiple individuals who met diagnostic criteria for neurofibromatosis 1 (NF1), including three individuals from the same family (Cunha KS et al. Genes (Basel), 2016 Dec;7:) and one unrelated individual with early-onset breast cancer before the age of 50 (Frayling IM et al. J Med Genet, 2019 04;56:209-219). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000534870 SCV003914728 pathogenic Neurofibromatosis, type 1 2023-04-11 criteria provided, single submitter clinical testing
Suma Genomics RCV000534870 SCV004244378 pathogenic Neurofibromatosis, type 1 criteria provided, single submitter clinical testing

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.