Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000204018 | SCV000262264 | uncertain significance | Charcot-Marie-Tooth disease, type 1C | 2019-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 160 of the LITAF protein (p.Arg160His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a LITAF-related disease. ClinVar contains an entry for this variant (Variation ID: 221090). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV000235954 | SCV000293036 | uncertain significance | not provided | 2015-08-14 | criteria provided, single submitter | clinical testing | The R160H 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. This substitution occurs at a position that is conserved across species. However, the R160H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, and in silico analysis is inconsistent in its predictions as to whether or not the 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. |
| Molecular Genetics Laboratory, |
RCV001174230 | SCV001337357 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |