Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mayo Clinic Laboratories, |
RCV002261770 | SCV002542136 | uncertain significance | not provided | 2021-10-11 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003095898 | SCV003457825 | uncertain significance | Amyotrophic lateral sclerosis type 21 | 2022-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 167 of the MATR3 protein (p.Arg167Trp). 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. ClinVar contains an entry for this variant (Variation ID: 1693901). This variant has not been reported in the literature in individuals affected with MATR3-related conditions. This variant is present in population databases (rs138894013, gnomAD 0.01%). |
| Molecular Genetics, |
RCV003994419 | SCV004812572 | uncertain significance | Neurodegeneration | 2022-03-03 | criteria provided, single submitter | clinical testing | This sequence change in MATR3 is predicted to replace arginine with tryptophan at codon 167, p.(Arg167Trp). The arginine residue is highly conserved (100 vertebrates, UCSC), and is not located in an annotated functional domain. There is a large physicochemical difference between arginine and tryptophan. The highest population minor allele frequency in gnomAD v2.1 is 0.02% (3/16,252 alleles) in the African/African American population, all absent from the controls cohort. To our knowledge, this variant has not been reported in the literature in any individuals with MATR3-related disease. Multiple lines of computational evidence have conflicting predictions for the missense substitution (2/6 algorithms predict benign). Based on the classification scheme RMH Modified ACMG Guidelines v1.4.0, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting. |