ClinVar Miner

Submissions for variant NM_138773.4(SLC25A46):c.776T>G (p.Leu259Arg)

gnomAD frequency: 0.00003  dbSNP: rs150754737
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
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.
GeneDx 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.