ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.3365-109939C>T (rs766942777)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487952 SCV000241908 likely benign not provided 2020-12-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; This variant is in the shorter transcript of NRXN1 (NM_138735.2), and alters a residue that is predicted to be in the signal peptide of the beta-neurexin protein (Zweier et al., 2009); This variant is associated with the following publications: (PMID: 18179900, 24832020, 21424692, 22504536, 17034946, 28289584, 29221905, 18728070)
CeGaT Praxis fuer Humangenetik Tuebingen RCV000487952 SCV000575209 uncertain significance not provided 2016-11-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000720337 SCV000851214 uncertain significance History of neurodevelopmental disorder 2017-10-20 criteria provided, single submitter clinical testing The p.S14L variant (also known as c.41C>T), located in coding exon 1 of the NRXN1 gene, results from a C to T substitution at nucleotide position 41. The serine at codon 14 is replaced by leucine, an amino acid with dissimilar properties. In four separate studies, this alteration was detected in 5/944 individuals with ASD, ID, seizures, schizophrenia, and/or non syndromic ID; however, the phenotype of these individuals was variable. In addition, this alteration has been detected in 1/1330 controls (Camacho-Garcia RJ et al. Neurobiol. Dis., 2012 Jul;47:135-43; Yangngam S et al. Genet Test Mol Biomarkers, 2014 Jul;18:510-5; Gauthier J et al. Hum. Genet., 2011 Oct;130:563-73; Feng J et al. Neurosci. Lett., 2006 Nov;409:10-3). In one functional study, authors claimed that cell surface trafficking in COS cells containing this variant was not significantly different than cells containing wild type protein; however, details regarding this data were not provided (Gauthier J et al. Hum. Genet., 2011 Oct;130:563-73). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics,Fulgent Genetics RCV000764441 SCV000895498 uncertain significance Pitt-Hopkins-like syndrome 2; Schizophrenia 17 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001484117 SCV001688526 likely benign Pitt-Hopkins-like syndrome 2 2020-11-22 criteria provided, single submitter clinical testing

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