ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.1033G>A (p.Val345Ile)

gnomAD frequency: 0.00006  dbSNP: rs145832489
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000443284 SCV000518498 uncertain significance not provided 2023-05-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22936568, 23714751)
Invitae RCV000644714 SCV000766417 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-09-15 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 345 of the CNTNAP2 protein (p.Val345Ile). This variant is present in population databases (rs145832489, gnomAD 0.1%). 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: 380435). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV000644714 SCV001326003 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2018-02-28 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.
Fulgent Genetics, Fulgent Genetics RCV002480294 SCV002780447 uncertain significance Autism, susceptibility to, 15; Cortical dysplasia-focal epilepsy syndrome 2022-01-06 criteria provided, single submitter clinical testing

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