ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.676C>A (p.Leu226Met)

gnomAD frequency: 0.00010  dbSNP: rs372345438
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000734138 SCV000240855 uncertain significance not provided 2024-08-19 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18179895)
Labcorp Genetics (formerly Invitae), Labcorp RCV000532136 SCV000645123 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-10-18 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 226 of the CNTNAP2 protein (p.Leu226Met). This variant is present in population databases (rs372345438, 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: 205322). 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: "Possibly 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.
Eurofins Ntd Llc (ga) RCV000734138 SCV000862256 uncertain significance not provided 2018-07-12 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000532136 SCV001322010 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002054196 SCV002496060 uncertain significance Autism, susceptibility to, 15; Cortical dysplasia-focal epilepsy syndrome 2021-03-30 criteria provided, single submitter clinical testing CNTNAP2 NM_014141.5 exon 5 p.Leu226Met (c.676C>A): This variant has not been reported in the literature but is present in 0.02% (3/13640) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/7-147108272-C-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:205322). Evolutionary conservation suggests that this variant may not impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics RCV002362979 SCV002662398 uncertain significance Inborn genetic diseases 2024-08-27 criteria provided, single submitter clinical testing The c.676C>A (p.L226M) alteration is located in exon 5 (coding exon 5) of the CNTNAP2 gene. This alteration results from a C to A substitution at nucleotide position 676, causing the leucine (L) at amino acid position 226 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002054196 SCV002788276 uncertain significance Autism, susceptibility to, 15; Cortical dysplasia-focal epilepsy syndrome 2021-08-04 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV000734138 SCV005195708 uncertain significance not provided criteria provided, single submitter not provided

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