ClinVar Miner

Submissions for variant NM_005609.4(PYGM):c.1948C>T (p.Arg650Ter)

gnomAD frequency: 0.00002  dbSNP: rs114073621
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Lab, Nemours Children's Health, Delaware RCV000498994 SCV000590833 pathogenic Glycogen storage disease, type V 2016-01-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000498994 SCV001198745 pathogenic Glycogen storage disease, type V 2023-07-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 433147). This premature translational stop signal has been observed in individuals with glycogen storage disease type V (PMID: 17324573; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg650*) in the PYGM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PYGM are known to be pathogenic (PMID: 8316268, 16786513).
Neuberg Centre For Genomic Medicine, NCGM RCV000498994 SCV002073185 pathogenic Glycogen storage disease, type V criteria provided, single submitter clinical testing The stop gained p.R650* in PYGM (NM_005609.4) has been previously reported in affected individuals (Aquaron R et al,Bruno C et al). It has been submitted to ClinVar as Pathogenic. The p.R650* variant is observed in 1/18,392 (0.0054%) alleles from individuals of East Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function mutations have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000498994 SCV004207252 pathogenic Glycogen storage disease, type V 2024-03-27 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000498994 SCV005684096 pathogenic Glycogen storage disease, type V 2024-05-20 criteria provided, single submitter clinical testing
Natera, Inc. RCV000498994 SCV001461272 pathogenic Glycogen storage disease, type V 2020-09-16 no assertion criteria provided clinical testing
Gene Friend Way, National Innovation Center RCV003324712 SCV004013896 likely pathogenic See cases 2023-07-28 no assertion criteria provided clinical testing This sequence change creates a premature translational stop signal (p.Arg650*) in the PYGM gene. It is expected to result in an absent or disrupted protein product. This premature translational stop signal has been observed in individuals with glycogen storage disease type V (PMID: 17324573). Recent genetic and functional studies have identified a role of abnormal glycinergic signaling in Autism Spectrum Disorder (ASD) (PMID: 28270747). In our study, a child diagnosed with ASD is the carrier of this mutation and also PRNP (rs1799990).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.