Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001216518 | SCV001388319 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with proline at codon 14 of the CNTNAP2 protein (p.Leu14Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. 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 tolerated. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004690019 | SCV005185653 | uncertain significance | not specified | 2024-05-16 | criteria provided, single submitter | clinical testing | Variant summary: CNTNAP2 c.41T>C (p.Leu14Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.3e-05 in 153496 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.41T>C in individuals affected with Autism, Susceptibility To, 15 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 945796). Based on the evidence outlined above, the variant was classified as uncertain significance. |