Submissions for variant NM_018834.6(MATR3):c.254C>G (p.Ser85Cys)

dbSNP: rs121434591

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000517083	SCV000614054	pathogenic	not provided	2017-06-20	criteria provided, single submitter	clinical testing
Invitae	RCV000015039	SCV000653847	pathogenic	Amyotrophic lateral sclerosis type 21	2023-06-26	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects MATR3 function (PMID: 24686783). 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 expected to disrupt MATR3 protein function. ClinVar contains an entry for this variant (Variation ID: 14002). This missense change has been observed in individual(s) with autosomal dominant distal myopathy with variable vocal cord weakness, pharyngeal weakness and respiratory failure (PMID: 9837826, 19344878, 24686783, 25154462, 25677933, 25952333). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 85 of the MATR3 protein (p.Ser85Cys).
CeGaT Center for Human Genetics Tuebingen	RCV000517083	SCV001248350	pathogenic	not provided	2017-01-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000015039	SCV001428685	pathogenic	Amyotrophic lateral sclerosis type 21	2019-12-12	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000015039	SCV002017223	pathogenic	Amyotrophic lateral sclerosis type 21	2019-12-10	criteria provided, single submitter	clinical testing
OMIM	RCV000015039	SCV000035295	pathogenic	Amyotrophic lateral sclerosis type 21	2014-11-01	no assertion criteria provided	literature only
UniProtKB/Swiss-Prot	RCV000015039	SCV000091147	likely pathogenic	Amyotrophic lateral sclerosis type 21		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.