ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.2122G>T (p.Val708Phe)

gnomAD frequency: 0.00002  dbSNP: rs763122160
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000407463 SCV000467259 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2018-01-13 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.
Illumina Laboratory Services, Illumina RCV000306719 SCV000467260 uncertain significance Pitt-Hopkins-like syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000407463 SCV001210933 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 708 of the CNTNAP2 protein (p.Val708Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is present in population databases (rs763122160, ExAC 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: 359185). 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 C45"). 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.
GeneDx RCV001753836 SCV002006629 uncertain significance not provided 2019-04-04 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

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