Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000220408 | SCV000279665 | uncertain significance | not provided | 2015-12-23 | criteria provided, single submitter | clinical testing | The L284F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L284F variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L284F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar 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. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV003621521 | SCV004458002 | uncertain significance | 3-Methylglutaconic aciduria type 2 | 2024-07-27 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 284 of the TAZ protein (p.Leu284Phe). This variant is present in population databases (rs782523340, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with TAZ-related conditions. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |