ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.1382C>T (p.Pro461Leu)

gnomAD frequency: 0.00001  dbSNP: rs530674644
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
Eurofins Ntd Llc (ga) RCV000724087 SCV000224877 uncertain significance not provided 2014-09-08 criteria provided, single submitter clinical testing
GeneDx RCV000724087 SCV000536386 uncertain significance not provided 2017-01-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NRXN1 gene. The P501L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P501L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P501L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in Human Gene Mutation Database in association with NRXN1-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000549238 SCV000651809 uncertain significance Pitt-Hopkins-like syndrome 2 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 501 of the NRXN1 protein (p.Pro501Leu). This variant is present in population databases (rs530674644, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 193621). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Ambry Genetics RCV002517666 SCV003693502 uncertain significance Inborn genetic diseases 2022-10-13 criteria provided, single submitter clinical testing The c.1502C>T (p.P501L) alteration is located in exon 10 (coding exon 9) of the NRXN1 gene. This alteration results from a C to T substitution at nucleotide position 1502, causing the proline (P) at amino acid position 501 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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.