ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.682G>A (p.Gly228Arg)

dbSNP: rs371512835
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483093 SCV000570506 uncertain significance not provided 2016-06-01 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CNTNAP2 gene. The G228R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The G228R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001851204 SCV002227917 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-10-05 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 421332). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. This variant is present in population databases (rs371512835, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 228 of the CNTNAP2 protein (p.Gly228Arg).
Escayg Lab, Department of Human Genetics, Emory University RCV001553785 SCV001478474 uncertain significance Autism spectrum disorder; Epilepsy; Intellectual disability no assertion criteria provided research The Gly228Arg variant in CNTNAP2 was identified in a Pakistani family with epilepsy, intellectual disability and autism spectrum disorder and segregated with disease in all sequenced individuals. It is a non-conservative amino substitution and absent from gnomAD in a homozygous state. Conflicting predictions (CADD: "21.4", PolyPhen-2: "Probably Damaging", SIFT: "Tolerated", PROVEAN: "Deleterious") and lack of previous homozygous pathogenic missense variants in CNTNAP2 in association with disease status leave the clinical significance of this variant unknown.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.