ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.392del (p.Pro131fs) (rs1555449607)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000657181 SCV000861541 pathogenic not provided 2018-05-25 criteria provided, single submitter clinical testing
GeneDx RCV000657181 SCV000778902 pathogenic not provided 2018-05-12 criteria provided, single submitter clinical testing The c.392delC variant in the PMM2 gene has been reported previously, using alternate nomenclature c.398_399delC, in one individual with CDG-1a, however, it is unknown if this individual harbored a second PMM2 variant (Matthijs et al., 2000). The c.392delC variant causes a frameshift starting with codon Proline 131, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 23 of the new reading frame, denoted p.Pro131LeufsX23. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.392delC variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.392delC as a pathogenic variant.
Integrated Genetics/Laboratory Corporation of America RCV000781733 SCV000920012 likely pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2018-05-09 criteria provided, single submitter clinical testing Variant summary: PMM2 c.392delC (p.Pro131LeufsX23) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 31784 control chromosomes (ExAC). The variant, c.392delC, has been reported in the literature in at least one individual affected with Congenital Disorder of Glycosylation Type 1a (Matthijs_1999). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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.

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