Submissions for variant NM_002863.5(PYGL):c.2042A>G (p.Lys681Arg)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003625308	SCV004488787	uncertain significance	Glycogen storage disease, type VI	2023-01-04	criteria provided, single submitter	clinical testing	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 expected to disrupt PYGL protein function. 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. This variant disrupts the p.Lys681 amino acid residue in PYGL. Other variant(s) that disrupt this residue have been observed in individuals with PYGL-related conditions (PMID: 17705025; Invitae), which suggests that this may be a clinically significant amino acid residue. This missense change has been observed in individual(s) with PYGL-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 681 of the PYGL protein (p.Lys681Arg).