Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523893 | SCV000619559 | uncertain significance | not provided | 2017-07-26 | criteria provided, single submitter | clinical testing | The D234Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D234Y variant is not observed in large population cohorts (Lek et al., 2016). This variant is a non-conservative amino acid substitution, 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 that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with CNTNAP2-related disorders (Stenson et al., 2014). |
| Labcorp Genetics |
RCV001327369 | SCV001518443 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 234 of the CNTNAP2 protein (p.Asp234Tyr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of CNTNAP2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 450928). 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: "Probably 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. |
| Ambry Genetics | RCV002367737 | SCV002665732 | uncertain significance | Inborn genetic diseases | 2024-10-16 | criteria provided, single submitter | clinical testing | The c.700G>T (p.D234Y) alteration is located in exon 5 (coding exon 5) of the CNTNAP2 gene. This alteration results from a G to T substitution at nucleotide position 700, causing the aspartic acid (D) at amino acid position 234 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV000523893 | SCV004244488 | uncertain significance | not provided | 2023-11-15 | criteria provided, single submitter | clinical testing | PM2, PP3 |