Submissions for variant NM_000290.4(PGAM2):c.119G>A (p.Arg40Gln)

gnomAD frequency: 0.00032  dbSNP: rs140545494

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000634554	SCV000755874	uncertain significance	Glycogen storage disease type X	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 40 of the PGAM2 protein (p.Arg40Gln). This variant is present in population databases (rs140545494, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PGAM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 529224). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PGAM2 protein function with a negative predictive value of 80%. 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.
Illumina Laboratory Services, Illumina	RCV000634554	SCV001322019	uncertain significance	Glycogen storage disease type X	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001569652	SCV001793773	likely benign	not provided	2020-09-15	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27195159)
CeGaT Center for Human Genetics Tuebingen	RCV001569652	SCV004185433	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	PGAM2: BP4