ClinVar Miner

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

gnomAD frequency: 0.00025  dbSNP: rs199978276
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001705028 SCV000241871 likely benign not provided 2020-12-23 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000188261 SCV000596086 uncertain significance not specified 2017-05-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV002317132 SCV000850763 uncertain significance Inborn genetic diseases 2019-08-21 criteria provided, single submitter clinical testing The p.Q770H variant (also known as c.2310G>T), located in coding exon 11 of the NRXN1 gene, results from a G to T substitution at nucleotide position 2310. The glutamine at codon 770 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000764443 SCV000895500 uncertain significance Pitt-Hopkins-like syndrome 2; Chromosome 2p16.3 deletion syndrome 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000810957 SCV000951199 uncertain significance Pitt-Hopkins-like syndrome 2 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 770 of the NRXN1 protein (p.Gln770His). This variant is present in population databases (rs199978276, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 206232). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000764443 SCV003920305 uncertain significance Pitt-Hopkins-like syndrome 2; Chromosome 2p16.3 deletion syndrome 2022-10-24 criteria provided, single submitter clinical testing This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.03% (21/68024) (https://gnomad.broadinstitute.org/variant/2-50531384-C-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:206232). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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