Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001361862 | SCV001557852 | uncertain significance | Hereditary spastic paraplegia 11 | 2021-05-31 | criteria provided, single submitter | clinical testing | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SPG11-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with phenylalanine at codon 111 of the SPG11 protein (p.Tyr111Phe). The tyrosine residue is moderately conserved and there is a small physicochemical difference between tyrosine and phenylalanine. |
| Ambry Genetics | RCV002322325 | SCV002609058 | uncertain significance | Inborn genetic diseases | 2022-08-08 | criteria provided, single submitter | clinical testing | The p.Y111F variant (also known as c.332A>T), located in coding exon 2 of the SPG11 gene, results from an A to T substitution at nucleotide position 332. The tyrosine at codon 111 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |