ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.637G>A (p.Gly213Arg) (rs199561088)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766526 SCV000241898 uncertain significance not provided 2018-07-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NRXN1 gene. The G213R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G213R variant is observed in 17/107626 (0.02%) alleles from individuals of European background (Lek et al., 2016). The G213R 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, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory,University of Chicago RCV000188287 SCV000596075 uncertain significance not specified 2016-01-29 criteria provided, single submitter clinical testing
Invitae RCV000813276 SCV000953631 uncertain significance Pitt-Hopkins-like syndrome 2 2019-03-25 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 213 of the NRXN1 protein (p.Gly213Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs199561088, ExAC 0.03%). This variant has not been reported in the literature in individuals with NRXN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 206256). 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: "Possibly 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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