Submissions for variant NM_014141.6(CNTNAP2):c.3047G>A (p.Arg1016Gln)

gnomAD frequency: 0.00001  dbSNP: rs143879959

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001045251	SCV001209089	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2022-09-08	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1016 of the CNTNAP2 protein (p.Arg1016Gln). This variant is present in population databases (rs143879959, gnomAD 0.009%). 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: 842773). 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 C35"). 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.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV002468618	SCV002764598	uncertain significance	Autism, susceptibility to, 15	2022-11-26	criteria provided, single submitter	clinical testing	A heterozygous missense variation in exon 19 of the CNTNAP2 gene that results in the amino acid substitution of Glutamine for Arginine at codon 1016 (p.Arg1016Gln) was detected. This variant has not been reported in the 1000 genomes databases. The in silico prediction of the variant is damaging by LRT. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as variant of uncertain significance.