Submissions for variant NM_018834.6(MATR3):c.2504A>G (p.Asn835Ser)

gnomAD frequency: 0.00015  dbSNP: rs201165929

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000703755	SCV000453186	benign	Amyotrophic lateral sclerosis type 21	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000703755	SCV000832670	uncertain significance	Amyotrophic lateral sclerosis type 21	2024-01-09	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 835 of the MATR3 protein (p.Asn835Ser). This variant is present in population databases (rs201165929, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. 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: 351142). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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	RCV000703755	SCV003808293	uncertain significance	Amyotrophic lateral sclerosis type 21	2019-10-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003970018	SCV004787111	likely benign	MATR3-related condition	2023-08-23	criteria provided, single submitter	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).