ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.476C>T (p.Pro159Leu) (rs373070672)

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
GeneDx RCV000188268 SCV000241878 uncertain significance not provided 2017-03-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NRXN1 gene. The P159L variant has notbeen published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge.The P159L variant is observed in 9/60582 (0.01%) alleles from individuals of European Non-Finnishbackground (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). TheP159L variant is a semi-conservative amino acid substitution, which may impact secondary proteinstructure as these residues differ in some properties. This substitution occurs at a position that isconserved in mammals, and in silico analysis predicts this variant is probably damaging to the proteinstructure/function. However, missense variants in nearby residues have not been reported in HumanGene 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 apathogenic variant or a rare benign variant.
Invitae RCV000824466 SCV000965365 uncertain significance Pitt-Hopkins-like syndrome 2 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 159 of the NRXN1 protein (p.Pro159Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs373070672, ExAC 0.01%). This variant has not been reported in the literature in individuals with NRXN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 206239). 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: "Benign"; Align-GVGD: "Class C0"). 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.

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.