Submissions for variant NM_018834.6(MATR3):c.2234C>T (p.Ala745Val)

gnomAD frequency: 0.00015  dbSNP: rs199797401

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000696564	SCV000825128	uncertain significance	Amyotrophic lateral sclerosis type 21	2023-12-07	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 745 of the MATR3 protein (p.Ala745Val). This variant is present in population databases (rs199797401, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MATR3-related conditions. ClinVar contains an entry for this variant (Variation ID: 574594). 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 with a negative predictive value of 80%. 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.
Revvity Omics, Revvity	RCV000696564	SCV003808297	uncertain significance	Amyotrophic lateral sclerosis type 21	2019-05-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004735754	SCV005357439	likely benign	MATR3-related disorder	2024-03-26	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).