ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.325G>A (p.Val109Ile)

dbSNP: rs779979011
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492823 SCV000583202 uncertain significance not provided 2017-05-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NRXN1 gene. The V109I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V109I variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V109I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. 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.
Invitae RCV001060039 SCV001224700 uncertain significance Pitt-Hopkins-like syndrome 2 2023-10-19 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 109 of the NRXN1 protein (p.Val109Ile). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 430408). 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 tolerated. 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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