ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.208G>C (p.Gly70Arg)

dbSNP: rs758143699
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187245 SCV000240827 uncertain significance not provided 2013-09-16 criteria provided, single submitter clinical testing p.G70R:GGT>CGT: c.208G>C in CNTNAP2 gene (NM_014141.5). The Gly70Arg 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. This variant is a non-conservative amino acid substitution of an uncharged Glycine residue with a positively charged Arginine residue at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, to our knowledge, there are no reported missense mutations associated with epilepsy in this region of the protein.The variant is found in CHILD-EPI panel(s).
Invitae RCV000644731 SCV000766434 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2017-08-17 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CNTNAP2-related disease. ClinVar contains an entry for this variant (Variation ID: 205298). This variant is present in population databases (rs758143699, ExAC 0.009%). This sequence change replaces glycine with arginine at codon 70 of the CNTNAP2 protein (p.Gly70Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant also falls at the last nucleotide of exon 2 of the CNTNAP2 coding sequence, which is part of the consensus splice site for this exon. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098).

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