Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001989269 | SCV002282515 | uncertain significance | Amyotrophic lateral sclerosis type 21 | 2021-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 456 of the MATR3 protein (p.Thr456Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with MATR3-related conditions. This variant is present in population databases (rs748098389, ExAC 0.01%). |
| Ambry Genetics | RCV004045444 | SCV004903385 | uncertain significance | Inborn genetic diseases | 2024-01-29 | criteria provided, single submitter | clinical testing | The c.1366A>G (p.T456A) alteration is located in exon 11 (coding exon 7) of the MATR3 gene. This alteration results from a A to G substitution at nucleotide position 1366, causing the threonine (T) at amino acid position 456 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |