Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001298639 | SCV001487702 | uncertain significance | Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C | 2020-01-01 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with PLEKHG5-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 972 of the PLEKHG5 protein (p.Pro972Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |
| Ambry Genetics | RCV003382504 | SCV004089002 | uncertain significance | Inborn genetic diseases | 2023-08-28 | criteria provided, single submitter | clinical testing | The c.2915C>T (p.P972L) alteration is located in exon 20 (coding exon 19) of the PLEKHG5 gene. This alteration results from a C to T substitution at nucleotide position 2915, causing the proline (P) at amino acid position 972 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |