Total submissions: 2
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, |
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. |