Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000362326 | SCV000334258 | uncertain significance | not provided | 2015-09-03 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000638363 | SCV000759862 | likely pathogenic | Bardet-Biedl syndrome | 2023-10-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 394 of the TRIM32 protein (p.Arg394His). This variant is present in population databases (rs121434447, gnomAD 0.01%). This missense change has been observed in individuals with clinical features of limb-girdle muscular dystrophy (PMID: 17994549; Invitae). ClinVar contains an entry for this variant (Variation ID: 7353). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects TRIM32 function (PMID: 17994549, 19349376, 33296226). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Broad Center for Mendelian Genomics, |
RCV000007778 | SCV001164486 | uncertain significance | Sarcotubular myopathy | 2018-12-03 | criteria provided, single submitter | research | The heterozygous p.Arg394His variant in TRIM32 was identified by our study in the compound heterozygous state, with a VUS, in one individual with limb-girdle muscular dystrophy (LGMD). This variant has been identified in 0.003658% (9/246046) of chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs121434447). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro functional studies provide some evidence that the p.Arg394His variant may impact protein function by affecting its localization, homodimerization, and ubiquitin ligase activity (PMID: 19349376, 17994549). However, these types of assays may not accurately represent biological function. The p.Arg394His variant in TRIM32 has been reported in 2 individuals with LGMD in the literature (PMID: 17994549). This variant has also been reported in ClinVar (Variation ID: 7353). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PS3_Moderate (Richards 2015). |
| Baylor Genetics | RCV001334685 | SCV001527598 | uncertain significance | Bardet-Biedl syndrome 11 | 2018-02-13 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| OMIM | RCV000007778 | SCV000027979 | pathogenic | Sarcotubular myopathy | 2009-07-01 | no assertion criteria provided | literature only |