ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.772+1050C>A (rs367919055)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000117833 SCV000152103 uncertain significance not provided 2012-11-19 criteria provided, single submitter clinical testing
GeneDx RCV000117833 SCV000241905 uncertain significance not provided 2015-09-02 criteria provided, single submitter clinical testing The Q264K variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed with any significant frequency in approximately 5,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant likely does not alter the protein structure/function. However, the Q264K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. 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).
Invitae RCV000460863 SCV000552203 uncertain significance Pitt-Hopkins-like syndrome 2 2018-09-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 264 of the NRXN1 protein (p.Gln264Lys). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is present in population databases (rs367919055, ExAC 0.07%) but has not been reported in the literature in individuals with an NRXN1-related disease. ClinVar contains an entry for this variant (Variation ID: 129817). 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 C0"). 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.
Ambry Genetics RCV000720275 SCV000851152 uncertain significance History of neurodevelopmental disorder 2017-11-29 criteria provided, single submitter clinical testing Insufficient evidence;Rare (0.1%) in general population databases (dbsnp, esp, 1000 genomes)

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