Submissions for variant NM_002863.5(PYGL):c.1334T>C (p.Leu445Pro)

dbSNP: rs2050437440

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001211148	SCV001382673	likely pathogenic	Glycogen storage disease, type VI	2023-03-23	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 941372). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 445 of the PYGL protein (p.Leu445Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with glycogen storage disease (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 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.
Molecular Diagnostics Laboratory, Seoul National University Hospital	RCV001211148	SCV002754426	likely pathogenic	Glycogen storage disease, type VI	2022-11-21	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001211148	SCV005629305	likely pathogenic	Glycogen storage disease, type VI	2024-06-15	criteria provided, single submitter	clinical testing