Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000724043 | SCV000232514 | pathogenic | not provided | 2014-07-17 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000008146 | SCV000836724 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-06-22 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects PMM2 function (PMID: 9140401, 25355454). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 7707). This missense change has been observed in individuals with PMM2-congenital disorder of glycosylation (PMID: 9140401, 9497260, 11875054, 12905014, 23430838, 25355454). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 216 of the PMM2 protein (p.Asn216Ile). |
Pediatric Metabolic Diseases, |
RCV000008146 | SCV000998569 | likely pathogenic | PMM2-congenital disorder of glycosylation | criteria provided, single submitter | clinical testing | ||
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000008146 | SCV002500420 | pathogenic | PMM2-congenital disorder of glycosylation | 2022-03-02 | criteria provided, single submitter | clinical testing | Variant summary: PMM2 c.647A>T (p.Asn216Ile) 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 was absent in 251180 control chromosomes. c.647A>T has been reported in the literature in individuals affected with Congenital Disorder Of Glycosylation Type 1a. These data indicate that the variant may be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
3billion | RCV000008146 | SCV002572753 | pathogenic | PMM2-congenital disorder of glycosylation | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.93; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000007707). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 12905014). A different missense change at the same codon (p.Asn216Ser) has been reported to be associated with PMM2 -related disorder (PMID: 11058896). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
Laboratory of Medical Genetics, |
RCV000008146 | SCV002577412 | pathogenic | PMM2-congenital disorder of glycosylation | 2022-06-28 | criteria provided, single submitter | clinical testing | PS4, PM1, PM2, PM5, PP2, PP3, PP5 |
Baylor Genetics | RCV000008146 | SCV004205277 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-06-17 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000008146 | SCV000028351 | pathogenic | PMM2-congenital disorder of glycosylation | 2003-10-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000008146 | SCV002092446 | pathogenic | PMM2-congenital disorder of glycosylation | 2021-07-07 | no assertion criteria provided | clinical testing |