ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.3653C>T (p.Thr1218Met)

gnomAD frequency: 0.00003  dbSNP: rs201720955
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492983 SCV000582996 uncertain significance not provided 2019-06-27 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001359620 SCV001555495 uncertain significance Pitt-Hopkins-like syndrome 2 2023-05-09 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NRXN1 protein function. ClinVar contains an entry for this variant (Variation ID: 430235). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. This variant is present in population databases (rs201720955, gnomAD 0.008%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1258 of the NRXN1 protein (p.Thr1258Met).

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