Total submissions: 6
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 |
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, |
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 |
RCV000049999 | SCV000082408 | probable-pathogenic | Muscle eye brain disease | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. | |
Natera, |
RCV000049999 | SCV002089590 | pathogenic | Muscle eye brain disease | 2021-07-15 | no assertion criteria provided | clinical testing |