ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.3385G>C (p.Asp1129His)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003085603 SCV003462036 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-04-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1129 of the CNTNAP2 protein (p.Asp1129His). This variant is present in population databases (rs781236853, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of CNTNAP2-related conditions (PMID: 26350204). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects CNTNAP2 function (PMID: 22872700, 29788201). 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.
GeneDx RCV003332405 SCV004040139 likely pathogenic not provided 2024-07-31 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect, as variant causes protein misfolding, resulting in ER sequestration and reduction of axon growth in cortical neurons (PMID: 22872700, 29788201); Observed in individuals with intellectual disability and/or autism in published literature (PMID: 26350204, 18179895); This variant is associated with the following publications: (PMID: 29788201, 18179895, 22872700, 26350204)

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