Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000191976 | SCV000775601 | uncertain significance | Brown-Vialetto-van Laere syndrome 1 | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 135 of the SLC52A3 protein (p.Thr135Ala). This variant is present in population databases (rs527853872, gnomAD 0.009%). This missense change has been observed in individual(s) with Brown-Vialetto-Van Laere (BVVL) syndrome (PMID: 29053833). ClinVar contains an entry for this variant (Variation ID: 210031). 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 alanine 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 |
RCV001753593 | SCV001988430 | uncertain significance | not provided | 2021-04-07 | criteria provided, single submitter | clinical testing | Identified in the single heterozygous state in an individual with Brown-Vialetto-Van Laere syndrome, however it is unclear if this individual harbored a second SLC52A3 variant (Manole et al., 2017); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29053833, 26072523) |
| Ambry Genetics | RCV002354539 | SCV002619780 | uncertain significance | Inborn genetic diseases | 2020-10-08 | criteria provided, single submitter | clinical testing | The p.T135A variant (also known as c.403A>G), located in coding exon 1 of the SLC52A3 gene, results from an A to G substitution at nucleotide position 403. The threonine at codon 135 is replaced by alanine, an amino acid with similar properties. This variant has been detected in the heterozygous state in an individual with Brown-Vialetto-Van Laere syndrome (Manole A et al. Brain, 2017 11;140:2820-2837). This amino acid position is not well 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. |