ClinVar Miner

Submissions for variant NM_000151.4(G6PC1):c.821C>T (p.Ala274Val)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001225198 SCV001397439 likely pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2019-06-19 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 274 of the G6PC protein (p.Ala274Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs774212157, ExAC 0.004%). This variant has been observed in individual(s) with clinical features of glycogen storage disorder type 1a (GSD1a) (PMID: 24980439, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. 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: Possibly Damaging; Align-GVGD: Class C0). This variant disrupts the p.Ala274Val amino acid residue in G6PC. Other variant(s) that disrupt this residue have been observed in individuals with G6PC-related conditions (PMID: 29374762), which suggests that this may be a clinically significant amino acid residue. 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.

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