ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.1249G>T (p.Asp417Tyr) (rs147815978)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187177 SCV000240757 uncertain significance not provided 2018-07-03 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CNTNAP2 gene. The D417Y variant hasnot been published as a pathogenic variant, nor has it been reported as a benign variant to ourknowledge. The D417Y variant is observed in 9/111,478 (0.008%) alleles from individuals ofEuropean background (Lek et al., 2016). The D417Y variant is a non-conservative amino acidsubstitution, which is likely to impact secondary protein structure as these residues differ in polarity,charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Aspartic acid are tolerated across species. In silico analysis predicts this variant is probably damaging to 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.
Invitae RCV000540016 SCV000645075 uncertain significance Pitt-Hopkins-like syndrome 1 2017-08-14 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 417 of the CNTNAP2 protein (p.Asp417Tyr). The aspartic acid residue is weakly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs147815978, ExAC 0.004%). This variant has not been reported in the literature in individuals with CNTNAP2-related disease. ClinVar contains an entry for this variant (Variation ID: 205236). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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.
Bioinformatics Core,Luxembourg Center for Systems Biomedicine RCV000656006 SCV000588282 pathogenic Rolandic epilepsy 2017-01-01 no assertion criteria provided case-control CAADphred>15

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