ClinVar Miner

Submissions for variant NM_017739.4(POMGNT1):c.1738C>T (p.Arg580Ter)

gnomAD frequency: 0.00001  dbSNP: rs386834018
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000049999 SCV000220156 likely pathogenic Muscle eye brain disease 2014-03-12 criteria provided, single submitter literature only
Labcorp Genetics (formerly Invitae), Labcorp RCV000818740 SCV000959370 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 2023-08-10 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: 56586). This premature translational stop signal has been observed in individuals with muscular dystrophy-dystroglycanopathy (PMID: 17906881, 19067344). This variant is present in population databases (rs386834018, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg580*) in the POMGNT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMGNT1 are known to be pathogenic (PMID: 19299310, 20816175, 21447391, 26908613, 27391550).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV002514264 SCV003761153 pathogenic Muscular dystrophy-dystroglycanopathy 2023-01-24 criteria provided, single submitter curation The p.Arg580Ter variant in POMGNT1 has been reported in two individuals with muscular dystrophy-dystroglycanopathy (PMID: 17906881, 19067344), and has been identified in 0.0009% (1/113260) European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs386834018). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#:56586) and has been interpreted as pathogenic by Invitae, Natera, Inc, and Juha Muilu Group (Institute for Molecular Medicine Finland (FIMM)) and likely pathogenic by Counsyl. In vitro functional studies provide some evidence that the p.Arg580Ter variant may impact protein function, as reflected by reduced catalytic activity in an in vitro enzymatic activity assay (PMID: 21361872). However, these types of assays may not accurately represent biological function. This nonsense variant leads to a premature termination codon at position 580, which is predicted to lead to a truncated or absent protein. Loss of function of the POMGNT1 gene is an established disease mechanism in autosomal recessive POMGNT1-associated muscular dystrophy-dystroglycanopathy. In summary, this variant meets criteria to be classified as pathogenic for POMGNT1-associated muscular dystrophy-dystroglycanopathy. ACMG/AMP Criteria applied: PVS1, PM2_supporting, PS3_Supporting (Richards 2015).
Baylor Genetics RCV003460641 SCV004205963 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 2024-03-16 criteria provided, single submitter clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049999 SCV000082408 probable-pathogenic Muscle eye brain disease no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Natera, Inc. RCV000049999 SCV002089590 pathogenic Muscle eye brain disease 2021-07-15 no assertion criteria provided clinical testing

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.