Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002025852 | SCV002288898 | uncertain significance | Hereditary spastic paraplegia 11 | 2022-07-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2034 of the SPG11 protein (p.Arg2034Gln). This variant is present in population databases (rs750101301, gnomAD 0.007%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 31475037). ClinVar contains an entry for this variant (Variation ID: 1503983). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine 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 | RCV002352735 | SCV002660505 | uncertain significance | Inborn genetic diseases | 2020-03-05 | criteria provided, single submitter | clinical testing | The p.R2034Q variant (also known as c.6101G>A), located in coding exon 32 of the SPG11 gene, results from a G to A substitution at nucleotide position 6101. The arginine at codon 2034 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not 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. |