ClinVar Miner

Submissions for variant NM_001135659.2(NRXN1):c.3166G>A (p.Gly1056Arg) (rs1553698219)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000533202 SCV000651822 uncertain significance Pitt-Hopkins-like syndrome 2 2017-06-08 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1056 of the NRXN1 protein (p.Gly1056Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with an NRXN1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on NRXN1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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