ClinVar Miner

Submissions for variant NM_018834.6(MATR3):c.2035A>G (p.Thr679Ala)

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
Invitae RCV003870567 SCV004675946 uncertain significance Amyotrophic lateral sclerosis type 21 2023-03-20 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MATR3 protein function. This variant has not been reported in the literature in individuals affected with MATR3-related conditions. This variant is present in population databases (rs758915987, gnomAD 0.002%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 679 of the MATR3 protein (p.Thr679Ala).
Molecular Genetics, Royal Melbourne Hospital RCV003994601 SCV004812814 uncertain significance Amyotrophic lateral sclerosis 2023-04-11 criteria provided, single submitter clinical testing This sequence change in MATR3 is predicted to replace threonine with alanine at codon 679, p.(Thr679Ala). The threonine residue is moderately conserved (62/80 vertebrates, UCSC), and is a predicted phosphothreonine residue. There is a small physicochemical difference between threonine and alanine. The highest population minor allele frequency in the population database gnomAD v2.1 is 0.002% (2/113,718 alleles) in the European (non-Finnish) population, which is consistent with an adult-onset neurodegenerative condition. To our knowledge, this variant has not been reported in the literature in any individuals. Multiple lines of computational evidence predict a benign effect for the missense substitution (6/6 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting, BP4.

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.