Submissions for variant NM_000303.3(PMM2):c.657G>C (p.Glu219Asp)

gnomAD frequency: 0.00039  dbSNP: rs144040842

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000370442	SCV000343455	uncertain significance	not provided	2016-06-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001116351	SCV001274418	uncertain significance	PMM2-congenital disorder of glycosylation	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae	RCV001116351	SCV001417456	uncertain significance	PMM2-congenital disorder of glycosylation	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 219 of the PMM2 protein (p.Glu219Asp). This variant is present in population databases (rs144040842, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with PMM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 289152). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PMM2 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.
Genetic Services Laboratory, University of Chicago	RCV001820835	SCV002068876	uncertain significance	not specified	2018-03-19	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001116351	SCV002776279	uncertain significance	PMM2-congenital disorder of glycosylation	2022-05-27	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000370442	SCV001951303	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000370442	SCV001963853	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000370442	SCV002034913	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001116351	SCV002092447	uncertain significance	PMM2-congenital disorder of glycosylation	2020-01-19	no assertion criteria provided	clinical testing