ClinVar Miner

Submissions for variant NM_002529.4(NTRK1):c.2312G>A (p.Arg771His)

gnomAD frequency: 0.00001  dbSNP: rs780724170
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 RCV001064041 SCV001228914 likely pathogenic Hereditary insensitivity to pain with anhidrosis 2023-05-30 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg765 amino acid residue in NTRK1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27265460, 27676246, 32219930). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NTRK1 protein function. ClinVar contains an entry for this variant (Variation ID: 858212). This variant is also known as Arg771His. This missense change has been observed in individual(s) with clinical features of NTRK1-related conditions and/or congenital insensitivity to pain with anhidrosis (PMID: 29770739, 31069529). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 765 of the NTRK1 protein (p.Arg765His).
Natera, Inc. RCV001064041 SCV001456806 uncertain significance Hereditary insensitivity to pain with anhidrosis 2020-09-16 no assertion criteria provided 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.