ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4331A>G (p.Lys1444Arg)

dbSNP: rs199474781
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001065767 SCV001230750 pathogenic Neurofibromatosis, type 1 2022-07-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Lys1423 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1568247, 11857752, 16786508, 23244495, 27322474). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects NF1 function (PMID: 8264648). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 68344). This missense change has been observed in individuals with neurofibromatosis, type 1 (PMID: 11735023, 12822827). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1423 of the NF1 protein (p.Lys1423Arg).
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001065767 SCV001479240 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001065767 SCV002560037 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV003466928 SCV004198353 pathogenic Juvenile myelomonocytic leukemia 2023-08-24 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059197 SCV000090726 not provided not provided no assertion provided not provided

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.