Submissions for variant NM_014141.6(CNTNAP2):c.400T>G (p.Trp134Gly)

gnomAD frequency: 0.00021  dbSNP: rs139694086

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000725056	SCV000240854	uncertain significance	not provided	2025-02-24	criteria provided, single submitter	clinical testing	Reported previously in the compound heterozygous state in a patient with multifocal epilepsy, moderate intellectual disability, autism spectrum disorder, ADHD, language impairment, and neuroimaging abnormalities; this patient also harbored variants in other genes (PMID: 37183190); 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: 37183190)
Eurofins Ntd Llc (ga)	RCV000725056	SCV000333609	uncertain significance	not provided	2018-01-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000476925	SCV000553434	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2024-01-07	criteria provided, single submitter	clinical testing	This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 134 of the CNTNAP2 protein (p.Trp134Gly). This variant is present in population databases (rs139694086, gnomAD 0.1%). This missense change has been observed in individual(s) with Pitt-Hopkins-like syndrome (PMID: 37183190). ClinVar contains an entry for this variant (Variation ID: 205321). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Athena Diagnostics	RCV000725056	SCV001143650	uncertain significance	not provided	2019-03-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000476925	SCV001320549	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Ambry Genetics	RCV002354522	SCV002621123	uncertain significance	Inborn genetic diseases	2021-07-13	criteria provided, single submitter	clinical testing	The c.400T>G (p.W134G) alteration is located in exon 3 (coding exon 3) of the CNTNAP2 gene. This alteration results from a T to G substitution at nucleotide position 400, causing the tryptophan (W) at amino acid position 134 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
St. Anna Children's Cancer Research Institute (CCRI)	RCV000476925	SCV003798979	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2023-02-08	criteria provided, single submitter	research	ACMG classification of pathogenicity variant 1: PM2, PP3
Mayo Clinic Laboratories, Mayo Clinic	RCV000725056	SCV004224118	uncertain significance	not provided	2023-04-12	criteria provided, single submitter	clinical testing	PP3