ClinVar Miner

Submissions for variant NM_138773.4(SLC25A46):c.803C>T (p.Thr268Met) (rs751900293)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483956 SCV000571892 likely pathogenic not provided 2016-10-19 criteria provided, single submitter clinical testing The T268M variant in the SLC25A46 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T268M variant was not observed 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 T268M 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. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. The T268M variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000559946 SCV000656083 uncertain significance Neuropathy, hereditary motor and sensory, type 6B 2019-02-05 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 268 of the SLC25A46 protein (p.Thr268Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs751900293, ExAC 0.009%). This variant has not been reported in the literature in individuals with an SLC25A46-related disease. ClinVar contains an entry for this variant (Variation ID: 422421). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on SLC25A46 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.