Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001909896 | SCV002184734 | uncertain significance | PMM2-congenital disorder of glycosylation | 2022-06-03 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1408282). 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. Experimental studies have shown that this missense change affects PMM2 function (PMID: 15844218). 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: "Probably Damaging"; Align-GVGD: "Class C15"). This missense change has been observed in individuals with congenital disorder of glycosylation type 1a (PMID: 15844218, 25497157). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 177 of the PMM2 protein (p.Gln177His). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001909896 | SCV005203867 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2024-07-02 | criteria provided, single submitter | clinical testing | Variant summary: PMM2 c.531G>C (p.Gln177His) 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 251488 control chromosomes. c.531G>C has been reported in the literature in compound heterozygous individuals affected with Congenital Disorder Of Glycosylation Type 1a (Le Bizec_2005, Dang Do_2023, Monin_2014). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal phosphomannomutase activity in transfected cells (Le Bizec_2005). The following publications have been ascertained in the context of this evaluation (PMID: 36719165, 15844218, 25497157). ClinVar contains an entry for this variant (Variation ID: 1408282). Based on the evidence outlined above, the variant was classified as likely pathogenic. |