Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001348322 | SCV001542622 | uncertain significance | Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 993 of the PLEKHG5 protein (p.Thr993Asn). This variant is present in population databases (rs769576836, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1044115). 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 | RCV002438808 | SCV002746219 | uncertain significance | Inborn genetic diseases | 2019-08-30 | criteria provided, single submitter | clinical testing | The p.T993N variant (also known as c.2978C>A), located in coding exon 19 of the PLEKHG5 gene, results from a C to A substitution at nucleotide position 2978. The threonine at codon 993 is replaced by asparagine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |