Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000806013 | SCV000945993 | uncertain significance | Hereditary spastic paraplegia 11 | 2022-05-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 5 of the SPG11 protein (p.Glu5Lys). This variant is present in population databases (no rsID available, gnomAD 0.02%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 32729724). ClinVar contains an entry for this variant (Variation ID: 650789). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The lysine 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 | RCV002388517 | SCV002700763 | uncertain significance | Inborn genetic diseases | 2019-09-16 | criteria provided, single submitter | clinical testing | The p.E5K variant (also known as c.13G>A), located in coding exon 1 of the SPG11 gene, results from a G to A substitution at nucleotide position 13. The glutamic acid at codon 5 is replaced by lysine, an amino acid with similar properties. This amino acid position is poorly 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. |