Submissions for variant NM_018834.6(MATR3):c.2301T>A (p.Asp767Glu)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003065426	SCV003458292	uncertain significance	Amyotrophic lateral sclerosis type 21	2022-11-23	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 767 of the MATR3 protein (p.Asp767Glu). 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 (rs748749843, gnomAD 0.002%).
PreventionGenetics, part of Exact Sciences	RCV004536569	SCV004115943	uncertain significance	MATR3-related disorder	2023-02-14	criteria provided, single submitter	clinical testing	The MATR3 c.2301T>A variant is predicted to result in the amino acid substitution p.Asp767Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-138661281-T-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.