ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.2290C>A (p.His764Asn)

gnomAD frequency: 0.00001  dbSNP: rs201446615
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187207 SCV000240788 uncertain significance not provided 2015-09-01 criteria provided, single submitter clinical testing p.His764Asn (CAC>AAC): c.2290 C>A in exon 15 of the CNTNAP2 gene (NM_014141.5). The H764N variant 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 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The H764N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, no missense mutations in nearby residues have been reported. 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).
Labcorp Genetics (formerly Invitae), Labcorp RCV001857606 SCV002178036 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2024-11-18 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 764 of the CNTNAP2 protein (p.His764Asn). This variant is present in population databases (rs201446615, gnomAD 0.004%). This missense change has been observed in individual(s) with Rolandic epilepsy or atypical Rolandic epilepsy (PMID: 29358611). ClinVar contains an entry for this variant (Variation ID: 205263). 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.
Bioinformatics Core, Luxembourg Center for Systems Biomedicine RCV000656008 SCV000588284 pathogenic Self-limited epilepsy with centrotemporal spikes 2017-01-01 no assertion criteria provided case-control CAADphred>15

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