ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.3167G>C (p.Ser1056Thr)

gnomAD frequency: 0.00002  dbSNP: rs776326011
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187226 SCV000240808 uncertain significance not provided 2014-01-22 criteria provided, single submitter clinical testing p.S1056T (AGC>ACC):c.3167G>C in CNTNAP2 gene (NM_014141.5). The Ser1056Thr missense change 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. Ser1056Thr alters a well conserved position in the Laminin G-like 4 domain of the CNTNAP2 protein. However, no other nearby missense mutations have been reported to our knowledge and this variant is a conservative substitution of one uncharged polar amino acid for another. In addition, in silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. The variant is found in CHILD-EPI panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001852451 SCV002304116 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2021-10-15 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with threonine at codon 1056 of the CNTNAP2 protein (p.Ser1056Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 205281).

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