Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001753913 | SCV001986333 | uncertain significance | not provided | 2019-11-29 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 21310273, 29054425, 21975507) |
Neurology Laboratory, |
RCV001733851 | SCV001984980 | pathogenic | Congenital myasthenic syndrome | 2021-08-22 | no assertion criteria provided | research | The Arg512Trp variant in GFPT1 has been reported in 1 Spain and 1 Senegal families with autosomal recessive inheritance, segregated with the disease in several affected relatives (Natera-de Benito et al., 2017; Senderek et al., 2011), and was absent from large population studies. Allele frequency of gnomAD Database is only 0.000003978.Additionally, in vitro functional study indicates that the Arg512Trp variant reduces the level of GFPT1 and O-GlcNAcylation (Senderek et al., 2011). In summary, the Arg512Trp variant meets our criteria to be classified as pathogenic (www.partners.org/personalizedmedicine/lmm) based upon low frequency variation, absence from controls, and functional evidence. |