ClinVar Miner

Submissions for variant NM_005271.5(GLUD1):c.1495G>A (p.Gly499Ser) (rs121909733)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000017504 SCV001378517 uncertain significance Hyperinsulinism-hyperammonemia syndrome 2019-09-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 499 of the GLUD1 protein (p.Gly499Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with HI/HA (PMID: 9571255, Invitae). ClinVar contains an entry for this variant (Variation ID: 16124). 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: Not Available; PolyPhen-2: Benign; Align-GVGD: Not Available). This variant disrupts the p.Gly499 amino acid residue in GLUD1. Other variant(s) that disrupt this residue have been observed in individuals with GLUD1-related conditions (PMID:10871207, 18928469, 9571255, 30352420, 19046187), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000017504 SCV000037776 pathogenic Hyperinsulinism-hyperammonemia syndrome 1998-05-07 no assertion criteria provided literature only

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