ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.4011G>C (p.Glu1337Asp) (rs200935246)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725076 SCV000241927 uncertain significance not provided 2014-10-06 criteria provided, single submitter clinical testing The E1377D variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved through mammals. However, the E1377D variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, and 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 this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725076 SCV000333801 uncertain significance not provided 2015-08-06 criteria provided, single submitter clinical testing
Invitae RCV000649738 SCV000771570 uncertain significance Pitt-Hopkins-like syndrome 2 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 1377 of the NRXN1 protein (p.Glu1377Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs200935246, ExAC 0.2%). This variant has been reported in individuals affected with intellectual disabilityand autism spectrum disorder (PMID: 24832020). ClinVar contains an entry for this variant (Variation ID: 206282). 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: "Benign"; Align-GVGD: "Class C15"). 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.
Fulgent Genetics,Fulgent Genetics RCV000764438 SCV000895495 uncertain significance Pitt-Hopkins-like syndrome 2; Schizophrenia 17 2018-10-31 criteria provided, single submitter clinical testing

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