Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001043665 | SCV001207423 | pathogenic | Limb-girdle muscular dystrophy-dystroglycanopathy, type C3; Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B3 | 2019-06-24 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in the last intron (intron 21) of the POMGNT1 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in several individuals affected with muscle-eye-brain disease who carry a second variant in the POMGNT1 gene (PMID: 28424332, 22554691, 15466003). ClinVar contains an entry for this variant (Variation ID: 56592). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. |
| Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000050005 | SCV000082414 | probable-pathogenic | Muscle eye brain disease | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. | |
| OMIM | RCV000240866 | SCV000299363 | pathogenic | Retinitis pigmentosa 76 | 2012-07-15 | no assertion criteria provided | literature only |