Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000544849 | SCV000656082 | uncertain significance | Neuropathy, hereditary motor and sensory, type 6B | 2022-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 259 of the SLC25A46 protein (p.Leu259Arg). This variant is present in population databases (rs150754737, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SLC25A46-related conditions. ClinVar contains an entry for this variant (Variation ID: 475801). 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. |
Gene |
RCV001559897 | SCV001782212 | uncertain significance | not provided | 2020-04-06 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002413632 | SCV002674914 | uncertain significance | Inborn genetic diseases | 2021-01-25 | criteria provided, single submitter | clinical testing | The p.L259R variant (also known as c.776T>G), located in coding exon 8 of the SLC25A46 gene, results from a T to G substitution at nucleotide position 776. The leucine at codon 259 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |