Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000236418 | SCV000292925 | uncertain significance | not provided | 2015-06-10 | criteria provided, single submitter | clinical testing | The P84L variant has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 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 P84L 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. However, in silico analysis is inconsistent in its predictions as to whether or not the P84L variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic or a rare benign variant. |
Labcorp Genetics |
RCV001857800 | SCV002149139 | uncertain significance | Charcot-Marie-Tooth disease type 1C | 2023-06-16 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 245794). This variant has not been reported in the literature in individuals affected with LITAF-related conditions. This variant is present in population databases (rs761746674, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 84 of the LITAF protein (p.Pro84Leu). |