ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.1997G>A (p.Ser666Asn)

gnomAD frequency: 0.00002  dbSNP: rs200098672
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187197 SCV000240777 uncertain significance not provided 2018-04-11 criteria provided, single submitter clinical testing p.Ser666Asn (AGC>AAC): c.1997 G>A in exon 13 of the CNTNAP2 gene (NM_014141.5). The Ser666Asn missense change 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. Ser666Asn alters a well conserved position in the CNTNAP2 protein. However, the amino acid substitution is conservative as both Serine and Asparagine are uncharged, polar amino acid residues. In addition, in silico analysis predicts this variant likely has a benign effect on protein structure/function. Therefore, based on the currently available information, it is unclear whether Ser666Asn is a disease-causing mutation or a rare benign variant. The variant is found in CHILD-EPI panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV002513996 SCV003325635 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-10-17 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 205254). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. This variant is present in population databases (rs200098672, gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 666 of the CNTNAP2 protein (p.Ser666Asn).

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