Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000645428 | SCV000767173 | uncertain significance | Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with proline at codon 466 of the PLEKHG5 protein (p.Ala466Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV002528915 | SCV003611304 | uncertain significance | Inborn genetic diseases | 2022-04-13 | criteria provided, single submitter | clinical testing | The c.1396G>C (p.A466P) alteration is located in exon 14 (coding exon 13) of the PLEKHG5 gene. This alteration results from a G to C substitution at nucleotide position 1396, causing the alanine (A) at amino acid position 466 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |