Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000483605 | SCV000574250 | uncertain significance | not provided | 2017-03-22 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SPG20 gene. The A23D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A23D variant is observed in 22/11548 (0.2%) alleles from individuals of Latino background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A23D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants have not been reported in Human Gene Mutation Database in association with SPG20-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000483605 | SCV001491256 | uncertain significance | not provided | 2021-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with aspartic acid at codon 23 of the SPART protein (p.Ala23Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is present in population databases (rs753340463, ExAC 0.2%). This variant has not been reported in the literature in individuals affected with SPART-related conditions. ClinVar contains an entry for this variant (Variation ID: 424442). 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 disruptive. 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. |
| Mayo Clinic Laboratories, |
RCV000483605 | SCV001713622 | uncertain significance | not provided | 2019-07-15 | criteria provided, single submitter | clinical testing |