ClinVar Miner

Submissions for variant NM_005609.4(PYGM):c.2392T>C (p.Trp798Arg) (rs119103258)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000081312 SCV000227678 pathogenic not provided 2012-07-11 criteria provided, single submitter clinical testing
GeneDx RCV000081312 SCV000491226 pathogenic not provided 2016-09-26 criteria provided, single submitter clinical testing The W798R variant in the PYGM gene has been reported previously, sometimes with alternate nomenclature of W797R, in the homozygous state, as well as the heterozygous state with a second variant of unknown phase, in multiple unrelated individuals with McArdle disease (Rubio et al., 2000; Fernandez et al., 2000; Martin et al., 2001; Rubio et al., 2007; Garcia-Consuegra, et al., 2009). The W798R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The W798R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In addition, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret W798R as a pathogenic variant.
Counsyl RCV000002402 SCV000677925 pathogenic Glycogen storage disease, type V 2015-07-29 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV000002402 SCV000803466 likely pathogenic Glycogen storage disease, type V 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Glycogen storage disease 5, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => Common mutation observed in multiple unrelated patients. (PMID:10590419,29143597,/10681080,14722619). PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:29143597). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product.
Fulgent Genetics,Fulgent Genetics RCV000002402 SCV000893903 likely pathogenic Glycogen storage disease, type V 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000002402 SCV001580144 pathogenic Glycogen storage disease, type V 2020-06-12 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with arginine at codon 798 of the PYGM protein (p.Trp798Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is present in population databases (rs119103258, ExAC 0.003%). This missense change has been observed to be homozygous or in combination with another PYGM variant in individuals affected with McArdle disease (PMID: 10590419,30415384,17994553,22250184,10681080). This variant is also known as W797R in the literature. ClinVar contains an entry for this variant (Variation ID: 2312). 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: Not Available; PolyPhen-2: Probably Damaging; Align-GVGD: Not Available). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002402 SCV000022560 pathogenic Glycogen storage disease, type V 2001-01-01 no assertion criteria provided literature only
GeneReviews RCV000002402 SCV000172201 pathogenic Glycogen storage disease, type V 2014-06-26 no assertion criteria provided literature only
Natera, Inc. RCV000002402 SCV001461268 pathogenic Glycogen storage disease, type V 2020-09-16 no assertion criteria provided clinical testing

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