Submissions for variant NM_005609.4(PYGM):c.614G>A (p.Gly205Asp)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003062398	SCV003439881	likely pathogenic	Glycogen storage disease, type V	2023-05-20	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 2137134). This missense change has been observed in individual(s) with McArdle disease (PMID: 21802952; Invitae). This variant is present in population databases (rs375724338, gnomAD 0.004%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 205 of the PYGM protein (p.Gly205Asp). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly205 amino acid residue in PYGM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8316268, 17221871, 17404776, 17630210, 19251976, 22818872). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 PYGM protein function.
Revvity Omics, Revvity	RCV003062398	SCV003810397	uncertain significance	Glycogen storage disease, type V	2022-12-22	criteria provided, single submitter	clinical testing