ClinVar Miner

Submissions for variant NM_001605.2(AARS1):c.2185C>T (p.Arg729Trp) (rs138081804)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000143804 SCV000294167 uncertain significance not provided 2018-05-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the AARS gene. The R729W variant has been previously reported in individuals with Charcot-Marie-Tooth disease; however it was also identified in 2/1090 normal control chromosomes (McLaughlin et al., 2012). It was subsequently reported as a variant of uncertain significance in an individual with CMT2; the patient was also found to have a variant in another gene and it was unclear if either variant was causative for the patient's phenotype (Lupo et al., 2016). The R729W variant is observed in 46/56252 (0.08%) alleles from individuals of European background, including one individual who was homozygous for the variant (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is not conserved. However, the R729W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001086355 SCV000553783 likely benign Charcot-Marie-Tooth disease, type 2 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000143804 SCV000608770 uncertain significance not provided 2018-11-01 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000143804 SCV000611067 uncertain significance not provided 2017-03-28 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre RCV000999712 SCV001156499 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001121845 SCV001280498 benign Charcot-Marie-Tooth disease, type 2N 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287479 SCV001474172 likely benign none provided 2020-04-10 criteria provided, single submitter clinical testing
Northcott Neuroscience Laboratory, ANZAC Research Institute RCV000143804 SCV000188697 non-pathogenic not provided no assertion criteria provided not provided Converted during submission to Benign.

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.