Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000671748 | SCV000796764 | uncertain significance | PMM2-congenital disorder of glycosylation | 2017-12-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000671748 | SCV001230003 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 42 of the PMM2 protein (p.Gly42Arg). This variant is present in population databases (rs755402538, gnomAD 0.003%). This missense change has been observed in individual(s) with congenital disorder of glycosylation type 1a (PMID: 12357336, 15844218). ClinVar contains an entry for this variant (Variation ID: 555844). 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%. 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. |
Gene |
RCV001756139 | SCV001985340 | uncertain significance | not provided | 2023-09-08 | criteria provided, single submitter | clinical testing | Reported heterozygous in an individual with CDG-1A and intermediated phosphomannomutase activity (Le Bizec et al., 2005); Reported in a patient with CDG-1a who also harbored a second missense variant (Schollen et al., 2002); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 15844218, 34426522, 16009061, 32457805, 35281664, 12357336) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001824863 | SCV002074458 | uncertain significance | not specified | 2022-01-28 | criteria provided, single submitter | clinical testing | Variant summary: PMM2 c.124G>A (p.Gly42Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 249876 control chromosomes (gnomAD). c.124G>A has been reported in the literature in compound heterozygous individuals affected with Congenital Disorder Of Glycosylation Type 1a (e.g. Schollen_2002, Tiwary_2022). In addition, Le Bizec et al (2005) describe a heterozygote individual with the variant exhibiting intermediate PMM activity. These data indicate that the variant may be associated with disease. Four ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
Fulgent Genetics, |
RCV000671748 | SCV002815739 | uncertain significance | PMM2-congenital disorder of glycosylation | 2022-02-16 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000671748 | SCV004205252 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2024-03-26 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000671748 | SCV001457165 | uncertain significance | PMM2-congenital disorder of glycosylation | 2020-09-16 | no assertion criteria provided | clinical testing |