Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001064453 | SCV001229357 | uncertain significance | Hereditary spastic paraplegia 11 | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with glutamine at codon 1983 of the SPG11 protein (p.Lys1983Gln). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamine. 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. ClinVar contains an entry for this variant (Variation ID: 858559). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV002355076 | SCV002655320 | uncertain significance | Inborn genetic diseases | 2020-05-19 | criteria provided, single submitter | clinical testing | The p.K1983Q variant (also known as c.5947A>C), located in coding exon 31 of the SPG11 gene, results from an A to C substitution at nucleotide position 5947. The lysine at codon 1983 is replaced by glutamine, 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. |