ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.1566C>T (p.Gly522=) (rs199701804)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188249 SCV000241859 uncertain significance not provided 2014-08-14 criteria provided, single submitter clinical testing The c.1686 C>T nucleotide substitution 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 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Multiple in silico models predict that the c.1686 C>T substitution could potentially create a new cryptic splice donor site that may supplant the natural site in exon 10 and lead to abnormal splicing. However, in the absence of RNA/functional studies, the actual effect of the c.1686 C>T sequence change is unknown. 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 RCV000695977 SCV000824518 uncertain significance Pitt-Hopkins-like syndrome 2 2018-05-11 criteria provided, single submitter clinical testing This sequence change affects codon 562 of the NRXN1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NRXN1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NRXN1-related disease. ClinVar contains an entry for this variant (Variation ID: 206220). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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