Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493274 | SCV000582217 | likely pathogenic | not provided | 2016-07-15 | criteria provided, single submitter | clinical testing | A P134L variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The P134L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (G132R and I138T) have been reported in the Human Gene Mutation Database in association with MSUD (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. |
| Labcorp Genetics |
RCV000984157 | SCV001200329 | pathogenic | Maple syrup urine disease | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 134 of the DBT protein (p.Pro134Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with maple syrup urine disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 429606). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DBT protein function. For these reasons, this variant has been classified as Pathogenic. |
| Genome- |
RCV000984157 | SCV002033179 | uncertain significance | Maple syrup urine disease | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000984157 | SCV001132162 | uncertain significance | Maple syrup urine disease | 2019-01-09 | no assertion criteria provided | clinical testing |