Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001881699 | SCV002151664 | uncertain significance | Hereditary spastic paraplegia 11 | 2021-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan with glycine at codon 2347 of the SPG11 protein (p.Trp2347Gly). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SPG11-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: "Deleterious"; PolyPhen-2: "Possibly 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 | RCV002370448 | SCV002667830 | uncertain significance | Inborn genetic diseases | 2021-01-05 | criteria provided, single submitter | clinical testing | The p.W2347G variant (also known as c.7039T>G), located in coding exon 39 of the SPG11 gene, results from a T to G substitution at nucleotide position 7039. The tryptophan at codon 2347 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |