ClinVar Miner

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

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487952 SCV000241908 uncertain significance not provided 2018-07-17 criteria provided, single submitter clinical testing The S14L variant has been reported in individuals with autism and seizures, although the phenotype was variable with reduced penetrance and did not uniformly include seizures (Feng et al., 2006; Gauthier et al., 2011; Yangngam et al., 2014). 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; Gauthier et al., 2011). Although the S14L was not observed in 1,201 controls studied separately (Feng et al., 2006; Gauthier et al., 2011; Kim et al., 2008), it was observed in 1/200 controls in an additional publication (Camacho-Garcia et al., 2012). This 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. However, this substitution occurs at a position that is not conserved, and functional studies have shown no abnormalities in beta-neurexin function as a result of the S14L variant (Gauthier et al., 2011). In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether S14L is a pathogenic variant or a rare benign variant.
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 Insufficient evidence
Fulgent Genetics,Fulgent Genetics RCV000764441 SCV000895498 uncertain significance Pitt-Hopkins-like syndrome 2; Schizophrenia 17 2018-10-31 criteria provided, single submitter clinical testing

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