ClinVar Miner

Submissions for variant NM_018834.6(MATR3):c.254C>G (p.Ser85Cys) (rs121434591)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517083 SCV000614054 pathogenic not provided 2017-06-20 criteria provided, single submitter clinical testing
Invitae RCV000015039 SCV000653847 pathogenic Amyotrophic lateral sclerosis 21 2016-10-31 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 85 of the MATR3 protein (p.Ser85Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases (rs121434591, ExAC no frequency). This variant has been reported to segregate in several families affected with autosomal dominant distal myopathy with variable vocal cord weakness, pharyngeal weakness and respiratory failure (PMID: 9837826, 19344878, 24686783, 25677933, 25952333, 25154462). Experimental studies have shown that this missense change was expressed at lower steady state levels, suggesting a structural effect of the mutation which is correlated with a change in affinity for the RNA binding protein TDP-43 (PMID: 24686783). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik 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 21 2019-12-12 criteria provided, single submitter clinical testing
OMIM RCV000015039 SCV000035295 pathogenic Amyotrophic lateral sclerosis 21 2014-11-01 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000015039 SCV000091147 likely pathogenic Amyotrophic lateral sclerosis 21 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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