Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000056837 | SCV002030930 | pathogenic | not provided | 2021-12-06 | criteria provided, single submitter | clinical testing | Published functional studies suggest a damaging effect (Boczek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23149175, 18217876, 27648269, 21533827, 21917775) |
Invitae | RCV000056837 | SCV002169723 | pathogenic | not provided | 2021-02-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg376 amino acid residue in GFAP. Other variant(s) that disrupt this residue have been observed in individuals with GFAP-related conditions (PMID: 21917775), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this variant affects GFAP protein function (PMID: 27648269). This variant has been observed in individual(s) with Alexander disease (PMID: 18217876, 21533827, 23149175, 27468269, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 66443). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 376 of the GFAP protein (p.Arg376Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. |
Epithelial Biology; Institute of Medical Biology, |
RCV000056837 | SCV000087950 | not provided | not provided | no assertion provided | not provided | ||
Gene |
RCV000192177 | SCV000223043 | not provided | Alexander disease | no assertion provided | literature only |