Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002314368 | SCV000847839 | uncertain significance | Inborn genetic diseases | 2016-09-14 | criteria provided, single submitter | clinical testing | The p.Q1183H variant (also known as c.3549G>C), located in coding exon 22 of the CNTNAP2 gene, results from a G to C substitution at nucleotide position 3549. The glutamine at codon 1183 is replaced by histidine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Invitae | RCV001862023 | SCV002163994 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with histidine at codon 1183 of the CNTNAP2 protein (p.Gln1183His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). 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: 588272). 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: "Possibly 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. |