Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000236620 | SCV000294295 | uncertain significance | Charcot-Marie-Tooth disease, type 2 | 2017-03-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 681 of the GARS protein (p.Pro681Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a GARS-related disease. ClinVar contains an entry for this variant (Variation ID: 246654). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
Mayo Clinic Genetic Testing Laboratories, |
RCV000660607 | SCV000782723 | uncertain significance | Charcot-Marie-Tooth disease type 2D; Distal hereditary motor neuronopathy type 5 | 2017-08-11 | criteria provided, single submitter | clinical testing |