Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000790723 | SCV000232042 | pathogenic | not provided | 2013-02-05 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000179744 | SCV000696501 | pathogenic | PMM2-congenital disorder of glycosylation | 2016-05-16 | criteria provided, single submitter | clinical testing | Variant summary: The PMM2 c.623G>C (p.Gly208Ala) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome. This variant was found in 1/121408 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic PMM2 variant (0.005902). This variant has been reported in multiple CDG1A patients homozygously or as a compound heterozygotes with a pathogenic variant (such as R141H) in trans. All reported patients had very low level of PMM activity detected. In addition, one clinical diagnostic laboratory classified this variant as pathogenic. Considering all, this variant is classified as pathogenic. |
Counsyl | RCV000179744 | SCV000789849 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2017-02-24 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000179744 | SCV000948400 | pathogenic | PMM2-congenital disorder of glycosylation | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 208 of the PMM2 protein (p.Gly208Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PMM2-CDG (PMID: 9497260, 10801058, 15277997, 24037084). ClinVar contains an entry for this variant (Variation ID: 92804). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Rady Children's Institute for Genomic Medicine, |
RCV000179744 | SCV000996185 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2018-08-13 | criteria provided, single submitter | clinical testing | This variant has been previously reported in the compound heterozygous state in individuals with Congenital disorder of glycosylation Type 1A (PMID: 9497260, 19396570, 10801058) and has been classified as pathogenic and likely pathogenic by multiple clinical diagnostic laboratories in ClinVar (Variation ID: 92804). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.623G>C (p.Gly208Ala) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.623G>C (p.Gly208Ala) variant is classified as Likely Pathogenic. |
Baylor Genetics | RCV000179744 | SCV004205263 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2023-09-01 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000179744 | SCV001457178 | pathogenic | PMM2-congenital disorder of glycosylation | 2020-09-16 | no assertion criteria provided | clinical testing |