ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.2190G>T (p.Gln730His) (rs199978276)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000719892 SCV000850763 uncertain significance History of neurodevelopmental disorder 2016-09-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Fulgent Genetics,Fulgent Genetics RCV000764443 SCV000895500 uncertain significance Pitt-Hopkins-like syndrome 2; Schizophrenia 17 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000188261 SCV000241871 uncertain significance not specified 2017-06-27 criteria provided, single submitter clinical testing The Q770H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q770H variant was not observed with any significant frequency in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The Q770H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the 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 RCV000188261 SCV000596086 uncertain significance not specified 2017-05-25 criteria provided, single submitter clinical testing
Invitae RCV000810957 SCV000951199 uncertain significance Pitt-Hopkins-like syndrome 2 2018-12-12 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 770 of the NRXN1 protein (p.Gln770His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs199978276, 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: 206232). 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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