ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.61C>T (p.Arg21Trp)

dbSNP: rs758340382
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000173104 SCV000224189 uncertain significance not provided 2014-06-10 criteria provided, single submitter clinical testing
Counsyl RCV000669624 SCV000794396 uncertain significance PMM2-congenital disorder of glycosylation 2017-09-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000669624 SCV000941708 uncertain significance PMM2-congenital disorder of glycosylation 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 21 of the PMM2 protein (p.Arg21Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs758340382, ExAC 0.02%). This missense change has been observed in individual(s) with clinical features of PMM2-related conditions (Invitae; https//www.omicsonline.org/clinical-and-molecular-features-of-patients-with-congenital-disorders-of-glycosylation-in-brazil-2161-0665.S3-001.pdf). ClinVar contains an entry for this variant (Variation ID: 193080). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg21 amino acid residue in PMM2. Other variant(s) that disrupt this residue have been observed in individuals with PMM2-related conditions (PMID: 23430905), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002516577 SCV003567893 uncertain significance Inborn genetic diseases 2021-09-28 criteria provided, single submitter clinical testing (Al Teneiji, 2017) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000669624 SCV004204837 likely pathogenic PMM2-congenital disorder of glycosylation 2023-10-17 criteria provided, single submitter clinical testing
GeneDx RCV000173104 SCV005327878 uncertain significance not provided 2023-07-02 criteria provided, single submitter clinical testing Not observed at 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: 23430905, 19862844, 34859900, 28122681, Brum2011[casereport])

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