ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.2533C>T (p.His845Tyr) (rs199784139)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000716693 SCV000847536 uncertain significance History of neurodevelopmental disorder 2018-01-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513409 SCV000608937 uncertain significance not provided 2017-06-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000513409 SCV000704629 uncertain significance not provided 2016-12-14 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764442 SCV000895499 uncertain significance Pitt-Hopkins-like syndrome 2; Schizophrenia 17 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000513409 SCV000241886 uncertain significance not provided 2018-07-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NRXN1 gene. The H885Y variant has been reported in a proband with autism spectrum disorder, his brother with learning disabilities, and their unaffected father; none had any known history of epilepsy (Jiang et al., 2013). The H885Y variant is observed in 132/125914 (0.10%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). The H885Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory, University of Chicago RCV000188275 SCV000596082 uncertain significance not specified 2015-09-22 criteria provided, single submitter clinical testing
Invitae RCV000465496 SCV000552204 uncertain significance Pitt-Hopkins-like syndrome 2 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 885 of the NRXN1 protein (p.His885Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs199784139, ExAC 0.1%). This variant has been reported in 2 brothers, one affected with autism spectrum disorder and the other with learning disability, and the variant was inherited from the unaffected father (PMID: 23849776). ClinVar contains an entry for this variant (Variation ID: 206245). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role 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.