ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.323C>T (p.Ala108Val)

gnomAD frequency: 0.00001  dbSNP: rs200503569
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000078587 SCV000230062 likely pathogenic not provided 2013-08-30 criteria provided, single submitter clinical testing
GeneDx RCV000078587 SCV000617239 pathogenic not provided 2022-07-01 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11058895, 9781052, 15771971, 9497260, 9425221, 9140401, 25497157, 25355454, 15844218, 34234304, 34480478)
Labcorp Genetics (formerly Invitae), Labcorp RCV000178072 SCV000938657 pathogenic PMM2-congenital disorder of glycosylation 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 108 of the PMM2 protein (p.Ala108Val). This variant is present in population databases (rs200503569, gnomAD 0.003%). This missense change has been observed in individual(s) with PMM2-related conditions (PMID: 9140401, 15844218, 25355454). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 92800). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PMM2 protein function. For these reasons, this variant has been classified as Pathogenic.
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano RCV001270234 SCV001364365 pathogenic Premature ovarian failure 2020-03-02 criteria provided, single submitter research
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris RCV000178072 SCV001519165 pathogenic PMM2-congenital disorder of glycosylation 2021-01-04 criteria provided, single submitter research
Myriad Genetics, Inc. RCV000178072 SCV002060161 likely pathogenic PMM2-congenital disorder of glycosylation 2021-11-10 criteria provided, single submitter clinical testing NM_000303.2(PMM2):c.323C>T(A108V) is a missense variant classified as likely pathogenic in the context of congenital disorder of glycosylation type Ia. A108V has been observed in cases with relevant disease (PMID: 32635232, Gurtunca_2013 _(no PMID; abstract), 25355454, 25497157, 15844218). Functional assessments of this variant are not available in the literature. A108V has been observed in population frequency databases (gnomAD: NFE 0.002%). In summary, NM_000303.2(PMM2):c.323C>T(A108V) is a missense variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Fulgent Genetics, Fulgent Genetics RCV000178072 SCV002803300 likely pathogenic PMM2-congenital disorder of glycosylation 2021-08-12 criteria provided, single submitter clinical testing
Baylor Genetics RCV000178072 SCV004205264 pathogenic PMM2-congenital disorder of glycosylation 2024-03-12 criteria provided, single submitter clinical testing

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