Submissions for variant NM_014141.6(CNTNAP2):c.3271C>G (p.Leu1091Val)

gnomAD frequency: 0.00005  dbSNP: rs756994633

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484319	SCV000573343	uncertain significance	not provided	2020-05-14	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV001049118	SCV001213152	uncertain significance	Cortical dysplasia-focal epilepsy syndrome	2022-06-13	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1091 of the CNTNAP2 protein (p.Leu1091Val). This variant is present in population databases (rs756994633, gnomAD 0.02%). 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: 423625). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Fulgent Genetics, Fulgent Genetics	RCV002475947	SCV002793058	uncertain significance	Autism, susceptibility to, 15; Cortical dysplasia-focal epilepsy syndrome	2022-05-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000484319	SCV004161280	likely benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	CNTNAP2: BP4