ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.391C>G (p.Pro131Ala)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003064317 SCV003441817 pathogenic PMM2-congenital disorder of glycosylation 2022-06-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with PMM2-related conditions (PMID: 9140401, 15844218; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.06%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 131 of the PMM2 protein (p.Pro131Ala).
Ambry Genetics RCV003064318 SCV003564181 likely pathogenic Inborn genetic diseases 2021-05-26 criteria provided, single submitter clinical testing The c.391C>G (p.P131A) alteration is located in exon 5 (coding exon 5) of the PMM2 gene. This alteration results from a C to G substitution at nucleotide position 391, causing the proline (P) at amino acid position 131 to be replaced by an alanine (A). Based on data from the Genome Aggregation Database (gnomAD), the PMM2 c.391C>G alteration was observed in 0.0032% (1/31398) of total alleles studied. This alteration has been reported in patients with congenital disorder of glycosylation type 1a (Matthijs, 1997; Le Bizec, 2005). This amino acid position is highly conserved in available vertebrate species. The p.P131A alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.
Baylor Genetics RCV003064317 SCV005056377 likely pathogenic PMM2-congenital disorder of glycosylation 2023-11-19 criteria provided, single submitter clinical testing

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