ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.682G>T (p.Gly228Cys)

dbSNP: rs558826439
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000791923 SCV000931192 pathogenic PMM2-congenital disorder of glycosylation 2023-03-09 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with PMM2-congenital disorder of glycosylation (CDG-Ia) (PMID: 10527672, 11058895, 23045520, 25192236, 28425223). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly228 amino acid residue in PMM2. Other variant(s) that disrupt this residue have been observed in individuals with PMM2-related conditions (PMID: 11058895, 11058896), which suggests that this may be a clinically significant amino acid residue. 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) performed at Invitae indicates that this missense variant is expected to disrupt PMM2 protein function. ClinVar contains an entry for this variant (Variation ID: 639185). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 228 of the PMM2 protein (p.Gly228Cys).
CeGaT Center for Human Genetics Tuebingen RCV001091538 SCV001247657 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000791923 SCV002072518 likely pathogenic PMM2-congenital disorder of glycosylation 2022-01-06 criteria provided, single submitter clinical testing _x000D_ Criteria applied: PS4_MOD, PM3, PM2_SUP, PM5_SUP, PP3
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000791923 SCV004028587 likely pathogenic PMM2-congenital disorder of glycosylation 2023-07-25 criteria provided, single submitter clinical testing Variant summary: PMM2 c.682G>T (p.Gly228Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251268 control chromosomes (gnomAD). c.682G>T has been reported in the literature in individuals affected with Congenital Disorder Of Glycosylation Type 1a (examples: Matthijs_1999, Matthijs_2000, Coorg_2012, Vals_2017 Inci_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23045520, 33960646, 11058895, 10527672, 28425223). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV000791923 SCV004205288 pathogenic PMM2-congenital disorder of glycosylation 2023-04-18 criteria provided, single submitter clinical testing
Natera, Inc. RCV000791923 SCV002092449 likely pathogenic PMM2-congenital disorder of glycosylation 2021-03-17 no assertion criteria provided clinical testing

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