Submissions for variant NM_014141.6(CNTNAP2):c.1603G>A (p.Glu535Lys)

gnomAD frequency: 0.00002  dbSNP: rs76475298

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724038	SCV000225017	uncertain significance	not provided	2014-08-20	criteria provided, single submitter	clinical testing
GeneDx	RCV000724038	SCV000240769	uncertain significance	not provided	2020-04-14	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000530310	SCV000645083	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2022-06-13	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 535 of the CNTNAP2 protein (p.Glu535Lys). This variant is present in population databases (rs76475298, gnomAD 0.01%). 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: 193703). 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. 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.
Baylor Genetics	RCV000530310	SCV001529461	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2018-02-12	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories, Mayo Clinic	RCV000724038	SCV001715976	uncertain significance	not provided	2019-05-06	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000724038	SCV005195710	uncertain significance	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000724038	SCV001928394	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000724038	SCV001970192	likely benign	not provided		no assertion criteria provided	clinical testing