ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.3355C>T (p.Arg1119Cys)

gnomAD frequency: 0.00006  dbSNP: rs367664952
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000656839 SCV000227691 uncertain significance not provided 2015-11-11 criteria provided, single submitter clinical testing
GeneDx RCV000656839 SCV000240814 uncertain significance not provided 2023-07-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533, 22872700, 18179895)
Fulgent Genetics, Fulgent Genetics RCV000515351 SCV000611463 uncertain significance Autism, susceptibility to, 15; Cortical dysplasia-focal epilepsy syndrome 2022-01-28 criteria provided, single submitter clinical testing
Invitae RCV000801308 SCV000941080 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1119 of the CNTNAP2 protein (p.Arg1119Cys). This variant is present in population databases (rs367664952, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of CNTNAP2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 195509). 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 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.
Ambry Genetics RCV002321694 SCV002606170 uncertain significance Inborn genetic diseases 2017-10-14 criteria provided, single submitter clinical testing The p.R1119C variant (also known as c.3355C>T), located in coding exon 20 of the CNTNAP2 gene, results from a C to T substitution at nucleotide position 3355. The arginine at codon 1119 is replaced by cysteine, an amino acid with highly dissimilar properties. An alternate substitution at this position, p.R1119H, has been reported in two brothers with autism, as well as in their unaffected father; however clinical details were limited (Bakkaloglu B et al. Am. J. Hum. Genet., 2008 Jan;82:165-73). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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