ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.416A>G (p.Asn139Ser)

gnomAD frequency: 0.00003  dbSNP: rs370517200
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187251 SCV000240833 uncertain significance not provided 2024-08-16 criteria provided, single submitter clinical testing 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: 25621974, 27734276)
Labcorp Genetics (formerly Invitae), Labcorp RCV000459034 SCV000553435 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 139 of the CNTNAP2 protein (p.Asn139Ser). This variant is present in population databases (rs370517200, gnomAD 0.006%). This missense change has been observed in individual(s) with early-onset epileptic encephalopathy (PMID: 27734276). ClinVar contains an entry for this variant (Variation ID: 205303). 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: "Probably Damaging"; 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.
Fulgent Genetics, Fulgent Genetics RCV000764695 SCV000895829 uncertain significance Autism, susceptibility to, 15; Cortical dysplasia-focal epilepsy syndrome 2018-10-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002265674 SCV002548478 uncertain significance not specified 2022-05-20 criteria provided, single submitter clinical testing Variant summary: CNTNAP2 c.416A>G (p.Asn139Ser) results in a conservative amino acid change located in the Coagulation factor 5/8 C-terminal domain (IPR000421) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251456 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.416A>G has been reported in the literature in one individual affected with Epilepsy (Gokben_2017), however, this report does not provide unequivocal conclusions about association of the variant with Pitt-Hopkins-Like Syndrome 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: the variant was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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.