Submissions for variant NM_000303.3(PMM2):c.728T>C (p.Leu243Pro)

dbSNP: rs2060937980

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Morava/Kozicz Lab, Department of Clinical Genomics, Mayo Clinic	RCV002261482	SCV002540746	likely pathogenic	PMM2-congenital disorder of glycosylation	2022-07-05	criteria provided, single submitter	clinical testing	The variant c.728T>C (p.Leu243Pro) is a missense substitution in exon 8 of8 that results in the alteration of the codon at amino acid position 243. The variant has not been listed in gnomAD or dbSNP. This variant has been previously reported as a disease-causing mutation by the Human Gene Mutation Database (HGMD, CM055486) with association with PMM2-CDG. In addition, the variant has been reported by Haeuptle et al, 2009 in a patient with CDG.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002261482	SCV003443487	pathogenic	PMM2-congenital disorder of glycosylation	2023-09-08	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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 PMM2 protein function. ClinVar contains an entry for this variant (Variation ID: 1693586). This missense change has been observed in individual(s) with PMM2-congenital disorder of glycosylation (CDG-Ia) (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 leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 243 of the PMM2 protein (p.Leu243Pro).