ClinVar Miner

Submissions for variant NM_001135659.2(NRXN1):c.3401A>G (p.Asn1134Ser) (rs201963074)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188291 SCV000241902 uncertain significance not provided 2013-09-30 criteria provided, single submitter clinical testing The Asn1134Ser missense change in the NRXN1 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. This variant is a conservative substitution of one uncharged, polar amino acid for another. However, it alters a highly conserved position in the Laminin G-like domain of the protein, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether Asn1134Ser is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000529852 SCV000651825 uncertain significance Pitt-Hopkins-like syndrome 2 2017-03-05 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 1134 of the NRXN1 protein (p.Asn1134Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs201963074, ExAC 0.01%) but has not been reported in the literature in individuals with a NRXN1-related disease. ClinVar contains an entry for this variant (Variation ID: 206260). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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