Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230976 | SCV003929284 | uncertain significance | not specified | 2023-04-25 | criteria provided, single submitter | clinical testing | Variant summary: MPI c.455G>A (p.Arg152Gln) results in a conservative amino acid change located in the phosphomannose isomerase type I, catalytic domain (IPR046457) of 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 2.4e-05 in 251468 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.455G>A has been reported in the literature as a biallelic genotype in at least three individuals affected with Congenital Disorder Of Glycosylation Type 1B (e.g. Schollen_2000, Schollen_2002, Penel-Capelle_2003, Janssen_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 (He_2014). When introduced into the mouse Mpi gene and expressed in a mpi-null yeast strain, the variant showed little to no damaging effect on MPI expression and activity versus WT. The following publications have been ascertained in the context of this evaluation (PMID: 24474243, 24982104, 12872847, 12357336, 10980531). 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 VUS-possibly pathogenic. |
| Baylor Genetics | RCV003466047 | SCV004193703 | likely pathogenic | MPI-congenital disorder of glycosylation | 2024-01-16 | criteria provided, single submitter | clinical testing |