ClinVar Miner

Submissions for variant NM_002047.4(GARS1):c.1171C>T (p.Arg391Cys) (rs370057212)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517891 SCV000613377 uncertain significance not specified 2017-06-30 criteria provided, single submitter clinical testing
Invitae RCV000653904 SCV000775794 uncertain significance Charcot-Marie-Tooth disease, type 2 2019-09-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 391 of the GARS protein (p.Arg391Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs370057212, ExAC 0.009%). This variant has been reported in an individual affected with Charcot Marie Tooth disease (PMID: 24078732). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Inherited Neuropathy Consortium RCV000789778 SCV000929162 likely benign Charcot-Marie-Tooth disease no assertion criteria provided literature only
Genesis Genome Database RCV000789778 SCV000999758 uncertain significance Charcot-Marie-Tooth disease 2019-08-14 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.