ClinVar Miner

Submissions for variant NM_000151.4(G6PC):c.161A>C (p.Gln54Pro) (rs1057517008)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411603 SCV000486578 likely pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2016-06-27 criteria provided, single submitter clinical testing
Invitae RCV000411603 SCV000931561 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2018-10-15 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 54 of the G6PC protein (p.Gln54Pro). The glutamine residue is weakly conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with glycogen storage disease type 1a (PMID: 10447271, 15542400). It has also been observed to segregate with disease in related individuals (PMID: 10447271, 15542400). ClinVar contains an entry for this variant (Variation ID: 371101). Experimental studies have shown that this missense change disrupts protein function (PMID: 11739393). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000411603 SCV001362493 pathogenic Glycogen storage disease due to glucose-6-phosphatase deficiency type IA 2019-06-07 criteria provided, single submitter clinical testing Variant summary: G6PC c.161A>C (p.Gln54Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251444 control chromosomes (gnomAD). The variant, c.161A>C, has been reported in the literature in multiple individuals affected with Glycogen Storage Disease Type Ia (Trioche_1999, Angaroni_2004). These data indicate that the variant is very likely to be associated with disease. One publication, Shieh_2002, reports G6Pase activity of this residual variant remained <10% of normal activity. One ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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