Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000056828 | SCV003442393 | pathogenic | not provided | 2023-05-08 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GFAP protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Tyr366 amino acid residue in GFAP. Other variant(s) that disrupt this residue have been observed in individuals with GFAP-related conditions (PMID: 17985264), which suggests that this may be a clinically significant amino acid residue. ClinVar contains an entry for this variant (Variation ID: 66434). This missense change has been observed in individual(s) with clinical features of Alexander disease (PMID: 15732097; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 366 of the GFAP protein (p.Tyr366His). |
| Epithelial Biology; Institute of Medical Biology, |
RCV000056828 | SCV000087941 | not provided | not provided | no assertion provided | not provided | ||
| Gene |
RCV000192167 | SCV000223033 | not provided | Alexander disease | no assertion provided | literature only |