Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000056823 | SCV003441990 | likely pathogenic | not provided | 2022-05-04 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 359 of the GFAP protein (p.Leu359Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of Alexander disease (PMID: 17509491, 17894839, 18388212). ClinVar contains an entry for this variant (Variation ID: 66430). 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"). This variant disrupts the p.Leu359 amino acid residue in GFAP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15732097, 22566711). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Epithelial Biology; Institute of Medical Biology, |
RCV000056823 | SCV000087936 | not provided | not provided | no assertion provided | not provided | ||
| Gene |
RCV000192161 | SCV000223026 | not provided | Alexander disease | no assertion provided | literature only |