ClinVar Miner

Submissions for variant NM_138387.3(G6PC3):c.376A>G (p.Met126Val)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820805 SCV000961533 uncertain significance Severe congenital neutropenia 4, autosomal recessive 2018-09-05 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 126 of the G6PC3 protein (p.Met126Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with G6PC3-related disease. Experimental studies have shown that this missense change does not affect G6PC3 protein expression or activity (PMID: 27611587). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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