Submissions for variant NM_014141.6(CNTNAP2):c.1238G>A (p.Ser413Asn)

dbSNP: rs796052371

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187176	SCV000240756	uncertain significance	not provided	2015-10-05	criteria provided, single submitter	clinical testing	p.Ser413Asn (AGT>AAT): c.1238 G>A in exon 8 of the CNTNAP2 gene (NM_014141.5). The Ser413Asn missense change in the CNTNAP2 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one uncharged, polar amino acid for another. It alters a position that is conserved in mammals; however, Asparagine is observed at this position in distantly related species. In silico analysis predicts this variant likely has a benign effect on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Ser413Asn is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Ambry Genetics	RCV002372145	SCV002662767	uncertain significance	Inborn genetic diseases	2020-03-20	criteria provided, single submitter	clinical testing	The p.S413N variant (also known as c.1238G>A), located in coding exon 8 of the CNTNAP2 gene, results from a G to A substitution at nucleotide position 1238. The serine at codon 413 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513994	SCV003272234	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2022-03-24	criteria provided, single submitter	clinical testing	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. 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 C0"). ClinVar contains an entry for this variant (Variation ID: 205235). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. This variant is present in population databases (rs796052371, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 413 of the CNTNAP2 protein (p.Ser413Asn).
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV003989498	SCV004806313	uncertain significance	Autism, susceptibility to, 15	2024-03-25	criteria provided, single submitter	clinical testing