ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.302C>G (p.Ala101Gly) (rs200184823)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188256 SCV000241866 uncertain significance not provided 2017-08-23 criteria provided, single submitter clinical testing The A101G variant in the NRXN1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A101G variant is observed in 6/5926 (0.101%) alleles from individuals in the ExAC dataset (Lek et al., 2016). The A101G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A101G as a variant of uncertain significance.
Ambry Genetics RCV000719147 SCV000850012 uncertain significance History of neurodevelopmental disorder 2018-04-05 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Fulgent Genetics,Fulgent Genetics RCV000764447 SCV000895504 uncertain significance Pitt-Hopkins-like syndrome 2; Schizophrenia 17 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000798181 SCV000937783 uncertain significance Pitt-Hopkins-like syndrome 2 2019-12-12 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 101 of the NRXN1 protein (p.Ala101Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine. This variant is present in population databases (rs200184823, ExAC 0.1%). This variant has not been reported in the literature in individuals with NRXN1-related disease. ClinVar contains an entry for this variant (Variation ID: 206227). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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