Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000187172 | SCV000240752 | uncertain significance | not provided | 2013-09-24 | criteria provided, single submitter | clinical testing | p.Ser367Pro (TCT>CCT): c.1099 T>C in CNTNAP2 gene (NM_014141.5). The Ser367Pro missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution of a polar Serine residue with a non-polar Proline residue and the gain of a Proline may affect the secondary structure of the CNTNAP2 protein. However, Ser367Pro alters a poorly conserved position in the protein and in silico analysis predicts this variant likely has a benign effect on the protein structure/function.Therefore, based on the currently available information, it is unclear whether Ser367Pro is a disease-causing mutation or a rare benign variant. The variant is found in CHILD-EPI panel(s). |
| Illumina Laboratory Services, |
RCV001163917 | SCV001326005 | uncertain significance | Cortical dysplasia-focal epilepsy syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |