Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001046364 | SCV001210263 | uncertain significance | Hereditary spastic paraplegia 11 | 2022-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2132 of the SPG11 protein (p.Met2132Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SPG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 843688). 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 not 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 | RCV002365685 | SCV002661147 | uncertain significance | Inborn genetic diseases | 2022-09-02 | criteria provided, single submitter | clinical testing | The p.M2132T variant (also known as c.6395T>C), located in coding exon 34 of the SPG11 gene, results from a T to C substitution at nucleotide position 6395. The methionine at codon 2132 is replaced by threonine, an amino acid with similar properties. This variant was identified in a cohort of African individuals with amyotrophic lateral sclerosis (Nel M et al. Neurol Genet, 2022 Feb;8:e654). This amino acid position is well 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. |