Submissions for variant NM_000290.4(PGAM2):c.28C>T (p.Arg10Trp)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002938781	SCV003269176	uncertain significance	Glycogen storage disease type X	2022-06-28	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 10 of the PGAM2 protein (p.Arg10Trp). This variant is present in population databases (rs529371882, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PGAM2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Ambry Genetics	RCV004067224	SCV005002527	uncertain significance	Inborn genetic diseases	2023-12-28	criteria provided, single submitter	clinical testing	The c.28C>T (p.R10W) alteration is located in exon 1 (coding exon 1) of the PGAM2 gene. This alteration results from a C to T substitution at nucleotide position 28, causing the arginine (R) at amino acid position 10 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV004823081	SCV005443434	uncertain significance	not provided	2024-07-04	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge