Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000008161 | SCV002511473 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2022-04-01 | criteria provided, single submitter | clinical testing | Variant summary: PMM2 c.677C>G (p.Thr226Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251300 control chromosomes. c.677C>G has been reported in the literature as compound heterozygous genotypes in individuals affected with Congenital Disorder Of Glycosylation Type 1a (example, Vuillaumier-Barrot_2000, de Lonlay_2001, Briones_2002, Quelhas_2021). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function example, Vuillaumier-Barrot_2000). The most pronounced variant effect results in 10%-<30% of normal Phosphomannomutase enzyme activity in-vitro. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV000008161 | SCV003441820 | pathogenic | PMM2-congenital disorder of glycosylation | 2021-12-03 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects PMM2 function (PMID: 10922383). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). ClinVar contains an entry for this variant (Variation ID: 7722). This missense change has been observed in individual(s) with PMM2-related conditions (PMID: 10922383, 11156536, 17166182). This variant is present in population databases (rs80338706, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 226 of the PMM2 protein (p.Thr226Ser). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000008161 | SCV004205309 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-11-22 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000008161 | SCV000028366 | pathogenic | PMM2-congenital disorder of glycosylation | 2000-08-01 | no assertion criteria provided | literature only | |
| Gene |
RCV000008161 | SCV000040588 | not provided | PMM2-congenital disorder of glycosylation | no assertion provided | literature only |