ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.91T>C (p.Phe31Leu) (rs749720760)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000487831 SCV000575034 likely pathogenic not provided 2016-11-30 criteria provided, single submitter clinical testing
Counsyl RCV000675084 SCV000800589 uncertain significance Congenital disorder of glycosylation, type Ia 2017-09-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000487831 SCV000862509 uncertain significance not provided 2018-07-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780613 SCV000918031 uncertain significance not specified 2018-12-20 criteria provided, single submitter clinical testing Variant summary: PMM2 c.91T>C (p.Phe31Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.4e-05 in 242922 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in PMM2 causing Congenital Disorder of Glycosylation Type 1a (7.4e-05 vs 0.0056), allowing no conclusion about variant significance. The variant, c.91T>C, has been reported in the literature as a novel variant in one individual affected with Congenital Disorder of Glycosylation Type 1a with elevated levels of asialotransferrin and disialotransferrin and low tetrasialotransferrin by serum Transferrin isoelectric focussing (Teneiji_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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