Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Pediatric Metabolic Diseases, |
RCV001089469 | SCV000998573 | likely pathogenic | PMM2-congenital disorder of glycosylation | criteria provided, single submitter | clinical testing | ||
Pediatrics, |
RCV001089469 | SCV001451942 | pathogenic | PMM2-congenital disorder of glycosylation | 2020-11-01 | criteria provided, single submitter | clinical testing | The PMM2 variant c.349G>T p.(Gly117Cys) causes an amino acid change from Gly to Cys at position 117. The substitution is in close proximity to the highly conserved acceptor splice site. This variant is absent in population databases and in clinvar is submitted as a likely pathogenic. Algorithms developed to predict the effect of missense variants showed:PolyPhen: Probablydamaging; Align-GVGD: C0; SIFT: Deleterious; MutationTaster: Disease-causing; Conservation_nt: high; Conservation_aa: high 2/2 likely splice effect; |
Labcorp Genetics |
RCV001089469 | SCV002949674 | uncertain significance | PMM2-congenital disorder of glycosylation | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with cysteine at codon 117 of the PMM2 protein (p.Gly117Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PMM2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |