Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002995547 | SCV003297091 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 | 2022-01-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the POMGNT1 protein in which other variant(s) (p.Arg129Trp) have been determined to be pathogenic (PMID: 28688748, 30961548, 34324503; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Disruption of the initiator codon has been observed in individual(s) with congenital muscular dystrophy (PMID: 28688748). This variant is present in population databases (rs774349262, gnomAD 0.003%). This sequence change affects the initiator methionine of the POMGNT1 mRNA. The next in-frame methionine is located at codon 144. |