Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001894206 | SCV002120199 | uncertain significance | Hereditary spastic paraplegia 11 | 2021-10-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with serine at codon 1855 of the SPG11 protein (p.Leu1855Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. This variant is present in population databases (rs138009927, ExAC 0.004%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SPG11 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 | RCV002343899 | SCV002650890 | uncertain significance | Inborn genetic diseases | 2021-05-04 | criteria provided, single submitter | clinical testing | The p.L1855S variant (also known as c.5564T>C), located in coding exon 30 of the SPG11 gene, results from a T to C substitution at nucleotide position 5564. The leucine at codon 1855 is replaced by serine, an amino acid with 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. |