ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.28G>A (p.Gly10Ser)

gnomAD frequency: 0.00001  dbSNP: rs777530225
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 RCV000519914 SCV000622030 uncertain significance not provided 2017-10-31 criteria provided, single submitter clinical testing The G10S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge.This variant is observed in 5/9704 (0.05%) alleles from individuals of East Asian background, in largepopulation cohorts, including 1 homozygous individual undergoing testing at GeneDx (Lek et al.,2016). The G10S 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. This substitution occurs at a position where amino acids with similar properties to Glycine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently availableinformation, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV003509562 SCV004343543 uncertain significance Pitt-Hopkins-like syndrome 2 2023-12-03 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 10 of the NRXN1 protein (p.Gly10Ser). This variant is present in population databases (rs777530225, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of autosomal recessive Pitt-Hopkins-like syndrome (PMID: 31130284). ClinVar contains an entry for this variant (Variation ID: 453161). 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.

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.