ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.2047G>A (p.Glu683Lys)

dbSNP: rs372580822
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187198 SCV000240778 uncertain significance not provided 2022-12-28 criteria provided, single submitter clinical testing Identified in an individual from an epilepsy cohort, however, a second CNTNAP2 variant was not identified (Friedman et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29619247)
Invitae RCV000696952 SCV000825537 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 683 of the CNTNAP2 protein (p.Glu683Lys). This variant is present in population databases (rs372580822, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 205255). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002317085 SCV000851251 uncertain significance Inborn genetic diseases 2016-09-20 criteria provided, single submitter clinical testing The p.E683K variant (also known as c.2047G>A), located in coding exon 13 of the CNTNAP2 gene, results from a G to A substitution at nucleotide position 2047. The glutamic acid at codon 683 is replaced by lysine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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