ClinVar Miner

Submissions for variant NM_005609.4(PYGM):c.280C>T (p.Arg94Trp)

gnomAD frequency: 0.00001  dbSNP: rs370247862
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557171 SCV000626785 pathogenic Glycogen storage disease, type V 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 94 of the PYGM protein (p.Arg94Trp). This variant is present in population databases (rs370247862, gnomAD 0.006%). This missense change has been observed in individual(s) with McArdle disease (glycogen storage disease type V) (PMID: 12508303, 16786513, 17324573, 17404776, 19472443, 21802952, 22250184). 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: 456518). 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 PYGM protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects PYGM function (PMID: 12508303, 17324573, 17404776, 17994553, 22250184). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001540069 SCV001757907 pathogenic not provided 2019-04-18 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect This variant is associated with the following publications: (PMID: 22347505, 19472443, 29143597, 21802952, 17994553, 17324573, 16786513, 17221871, 12508303, 30316539)
Revvity Omics, Revvity RCV000557171 SCV002019573 pathogenic Glycogen storage disease, type V 2023-08-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000557171 SCV002809786 pathogenic Glycogen storage disease, type V 2021-09-12 criteria provided, single submitter clinical testing
Baylor Genetics RCV000557171 SCV004207240 pathogenic Glycogen storage disease, type V 2023-08-22 criteria provided, single submitter clinical testing
Natera, Inc. RCV000557171 SCV002092348 pathogenic Glycogen storage disease, type V 2021-06-10 no assertion criteria provided clinical testing

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