ClinVar Miner

Submissions for variant NM_005918.4(MDH2):c.421G>A (p.Ala141Thr)

gnomAD frequency: 0.00001  dbSNP: rs782204186
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
Baylor Genetics RCV001331491 SCV001523535 uncertain significance Developmental and epileptic encephalopathy, 51 2019-03-27 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001863244 SCV002239601 uncertain significance not provided 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 141 of the MDH2 protein (p.Ala141Thr). This variant is present in population databases (rs782204186, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MDH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1030035). 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 tolerated. 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.
Ambry Genetics RCV002329303 SCV002629025 uncertain significance Inborn genetic diseases 2022-10-11 criteria provided, single submitter clinical testing The p.A141T variant (also known as c.421G>A), located in coding exon 4 of the MDH2 gene, results from a G to A substitution at nucleotide position 421. The alanine at codon 141 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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.

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.