ClinVar Miner

Submissions for variant NM_004130.3(GYG1):c.487del (p.Asp163fs) (rs727502871)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599598 SCV000709809 pathogenic not provided 2018-12-04 criteria provided, single submitter clinical testing The c.487delG variant has been reported in individuals with variable muscle weakness, cardiac arrhythmia, and accumulation of glycogenin-1 in muscle and heart who also had a second GYG1 variant identified (Moslemi et al. 2010; Hedberg-Oldfors et al., 2017; Desikan et al., 2018). The c.487delG variant is observed in 110/277114 (0.04%) alleles in large population cohorts and no individuals are reported to be homozygous (Lek et al., 2016). The deletion causes a frameshift starting with codon Aspartic Acid 163, changes this amino acid to a Threonine residue and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Asp163ThrfsX5. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret c.487delG as pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000599598 SCV000855156 pathogenic not provided 2017-08-16 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150102 SCV000967669 pathogenic Polyglucosan body myopathy 2 2018-09-12 criteria provided, single submitter clinical testing The p.Asp163ThrfsX5 variant in GYG1 has been reported in 2 homozygous and 2 comp ound heterozygous individuals with clinical features of polyglucosan body myopat hy 2 and segregated in the compound heterozygous state in 1 affected relative ( Ben Yaou 2017, Hedberg-Oldfors 2018, Krag 2017, Moslemi 2010). This variant has been identified in 0.076% (96/126642) of European chromosomes by the Genome Aggr egation Database (gnomAD, and reported in ClinV ar (Variation ID#162665). Although this variant has been seen in the general po pulation, its frequency is low enough to be consistent with a recessive carrier frequency. This variant is predicted to cause a frameshift, which alters the pro tein?s amino acid sequence beginning at position 163 and leads to a premature te rmination codon 5 amino acids downstream. This alteration is then predicted to l ead to a truncated or absent protein. Biallelic loss of function of the GYG1 gen e is strongly associated with polyglucosan body myopathy 2. In summary, this var iant meets criteria to be classified as pathogenic for polyglucosan body myopath y 2 in an autosomal recessive manner based upon probands, segregation, and pred icted impact on protein. ACMG/AMP Criteria applied: PVS1_Strong, PM3, PP1.
Undiagnosed Diseases Network,NIH RCV001090152 SCV001245600 pathogenic Glycogen storage disease XV 2019-09-17 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000599598 SCV001501885 pathogenic not provided 2021-01-01 criteria provided, single submitter clinical testing
OMIM RCV000150102 SCV000196926 pathogenic Polyglucosan body myopathy 2 2014-12-01 no assertion criteria provided literature only

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