ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.963C>A (p.Phe321Leu)

gnomAD frequency: 0.00012  dbSNP: rs765211652
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658313 SCV000780085 uncertain significance not provided 2018-05-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CNTNAP2 gene. The F321L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The F321L variant is observed in 12/34406 (0.04%) alleles from individuals of Latino background in large population cohorts (Lek et al., 2016). The F321L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001855371 SCV002182970 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2021-08-14 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 321 of the CNTNAP2 protein (p.Phe321Leu). The phenylalanine residue is weakly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs765211652, ExAC 0.001%). 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: 546436). 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.

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