ClinVar Miner

Submissions for variant NM_002055.5(GFAP):c.1126C>T (p.Arg376Trp)

dbSNP: rs267607512
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, Singapore RCV000056837 SCV000087950 not provided not provided no assertion provided not provided
GeneReviews RCV000192177 SCV000223043 not provided Alexander disease no assertion provided literature only

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