ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.421C>T (p.Arg141Cys) (rs746610168)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665622 SCV000789774 likely pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2017-02-17 criteria provided, single submitter clinical testing
Invitae RCV000665622 SCV000944707 likely pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 141 of the PMM2 protein (p.Arg141Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs746610168, ExAC 0.03%). This variant has been observed in an individual affected with a congenital disorder of glycosylation (PMID: 15844218). ClinVar contains an entry for this variant (Variation ID: 550780). This variant has been reported to affect PMM2 protein function (PMID: 15844218). This variant disrupts the p.Arg141 amino acid residue in PMM2. Other variant(s) that disrupt this residue have been observed in individuals with PMM2-related conditions (PMID: 9497260, 11517108, 21541725, 25355454, 19357119), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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