ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5561T>A (p.Leu1854Gln)

dbSNP: rs878853903
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
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001290820 SCV001478984 uncertain significance Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001290820 SCV001540839 uncertain significance Neurofibromatosis, type 1 2021-05-05 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces leucine with glutamine at codon 1833 of the NF1 protein (p.Leu1833Gln). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Leu1833 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
GeneDx RCV001751553 SCV002005431 uncertain significance not provided 2019-08-28 criteria provided, single submitter clinical testing Has not been previously published as a pathogenic or benign germline variant to our knowledge; A different missense change at this residue (Leu1833Pro) has been reported in individuals with suspected or clinically diagnosed Neurofibromatosis type 1 (Xu 2014, Pasmant 2015); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 29106415, 24789688, 25074460)
Genome-Nilou Lab RCV001290820 SCV002560882 uncertain significance Neurofibromatosis, type 1 2022-03-15 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.