ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.35T>G (p.Phe12Cys) (rs1298445857)

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
Ambry Genetics RCV000717333 SCV000848183 uncertain significance History of neurodevelopmental disorder 2016-11-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Invitae RCV000698366 SCV000827026 uncertain significance Pitt-Hopkins-like syndrome 2 2018-07-18 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with cysteine at codon 12 of the NRXN1 protein (p.Phe12Cys). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and cysteine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with NRXN1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.