ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.343A>C (p.Met115Leu)

gnomAD frequency: 0.00001  dbSNP: rs758526505
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480947 SCV000573491 uncertain significance not provided 2017-02-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CNTNAP2 gene. The M115L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M115L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The M115L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Baylor Genetics RCV001328715 SCV001519895 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2019-02-20 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV001328715 SCV003029553 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-07-15 criteria provided, single submitter clinical testing 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 423756). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. This variant is present in population databases (rs758526505, gnomAD 0.002%). This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 115 of the CNTNAP2 protein (p.Met115Leu).
Ambry Genetics RCV002526958 SCV003564203 uncertain significance Inborn genetic diseases 2021-05-16 criteria provided, single submitter clinical testing The c.343A>C (p.M115L) alteration is located in exon 3 (coding exon 3) of the CNTNAP2 gene. This alteration results from a A to C substitution at nucleotide position 343, causing the methionine (M) at amino acid position 115 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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