ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.205C>T (p.Pro69Ser)

dbSNP: rs769648248
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409367 SCV000486859 likely pathogenic PMM2-congenital disorder of glycosylation 2016-08-24 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000409367 SCV000992592 pathogenic PMM2-congenital disorder of glycosylation 2024-09-24 criteria provided, single submitter research ACMG codes: PS3_Strong, PS4_Strong, PM3_Strong, PM2
Labcorp Genetics (formerly Invitae), Labcorp RCV000409367 SCV001574940 pathogenic PMM2-congenital disorder of glycosylation 2024-12-12 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 69 of the PMM2 protein (p.Pro69Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of PMM2-related conditions (PMID: 22801829, 31391289). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 371307). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PMM2 protein function with a positive predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001545880 SCV001765295 likely pathogenic not provided 2025-03-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 31391289, 19862844, 10527672, 12357336, 15844218, 33413482, 34782856, 22801829, 11156536, 37224763, 32635232)
Baylor Genetics RCV000409367 SCV004205275 pathogenic PMM2-congenital disorder of glycosylation 2023-12-14 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000409367 SCV005641538 pathogenic PMM2-congenital disorder of glycosylation 2024-04-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV000409367 SCV002089472 likely pathogenic PMM2-congenital disorder of glycosylation 2020-12-15 no assertion criteria provided clinical testing

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