Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001224263 | SCV001396450 | uncertain significance | Hereditary spastic paraplegia 11 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with isoleucine at codon 2424 of the SPG11 protein (p.Val2424Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002379850 | SCV002669181 | uncertain significance | Inborn genetic diseases | 2019-09-26 | criteria provided, single submitter | clinical testing | The p.V2424I variant (also known as c.7270G>A), located in coding exon 40 of the SPG11 gene, results from a G to A substitution at nucleotide position 7270. The valine at codon 2424 is replaced by isoleucine, an amino acid with highly 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. |