Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000795720 | SCV000935191 | uncertain significance | Brown-Vialetto-van Laere syndrome 1 | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 167 of the SLC52A3 protein (p.Val167Ile). This variant is present in population databases (rs112034541, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SLC52A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 642283). 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 isoleucine 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. |
Gene |
RCV001759504 | SCV001996800 | uncertain significance | not provided | 2019-11-13 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23506902) |
Ambry Genetics | RCV002334480 | SCV002641759 | uncertain significance | Inborn genetic diseases | 2020-10-21 | criteria provided, single submitter | clinical testing | The p.V167I variant (also known as c.499G>A), located in coding exon 1 of the SLC52A3 gene, results from a G to A substitution at nucleotide position 499. The valine at codon 167 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not conserved however, isoleucine is a reference amino acid in several 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. |