Submissions for variant NM_014141.6(CNTNAP2):c.355G>A (p.Asp119Asn)

gnomAD frequency: 0.00004  dbSNP: rs777035367

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187250	SCV000240832	uncertain significance	not provided	2019-07-22	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV000548297	SCV000645110	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2022-03-15	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 119 of the CNTNAP2 protein (p.Asp119Asn). This variant is present in population databases (rs777035367, 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: 205302). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Illumina Laboratory Services, Illumina	RCV000548297	SCV001320548	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics	RCV003258688	SCV003950046	uncertain significance	Inborn genetic diseases	2023-04-20	criteria provided, single submitter	clinical testing	The c.355G>A (p.D119N) alteration is located in exon 3 (coding exon 3) of the CNTNAP2 gene. This alteration results from a G to A substitution at nucleotide position 355, causing the aspartic acid (D) at amino acid position 119 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.