Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000424845 | SCV000534563 | uncertain significance | not provided | 2016-12-22 | criteria provided, single submitter | clinical testing | The A191T variant in the SLC39A13 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A191T variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A191T 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. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, we interpret A191T as a variant of uncertain significance. |
| Invitae | RCV001047790 | SCV001211770 | uncertain significance | Ehlers-Danlos syndrome, spondylocheirodysplastic type | 2022-08-19 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 191 of the SLC39A13 protein (p.Ala191Thr). This variant is present in population databases (rs138998777, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with SLC39A13-related conditions. ClinVar contains an entry for this variant (Variation ID: 391481). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | RCV002522633 | SCV003710147 | likely benign | Inborn genetic diseases | 2022-09-06 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |