Submissions for variant NM_001605.3(AARS1):c.2185C>T (p.Arg729Trp)

gnomAD frequency: 0.00072  dbSNP: rs138081804

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000143804	SCV000294167	uncertain significance	not provided	2024-10-03	criteria provided, single submitter	clinical testing	Reported in individuals with Charcot-Marie-Tooth disease; however it was also identified in 2/1090 normal control chromosomes (PMID: 22009580); 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 (PMID: 26752306); Reported in an individual with axonal neuropathy; the R729W variant does not segregate with disease in the family as it was observed in both affected and unaffected family members and was absent in affected family members, and the patient was also found to have a variant in another gene that appears to segregate with disease in the family (PMID: 30642740); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32376792, 25817015, Elshiekh2020[article], 22009580, 26752306, 30642740)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086355	SCV000553783	likely benign	Charcot-Marie-Tooth disease type 2	2025-01-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics 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 Laboratory Services, Illumina	RCV001121845	SCV001280498	benign	Charcot-Marie-Tooth disease axonal 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	RCV000143804	SCV001474172	likely benign	not provided	2024-10-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002460928	SCV002755064	uncertain significance	Inborn genetic diseases	2023-10-31	criteria provided, single submitter	clinical testing	Unlikely to be causative of AARS-related Charcot-Marie-Tooth disease, type 2 (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Northcott Neuroscience Laboratory, ANZAC Research Institute	RCV000143804	SCV000188697	non-pathogenic	not provided		no assertion criteria provided	not provided	Converted during submission to Benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000143804	SCV001741092	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000143804	SCV001918414	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000143804	SCV001928775	likely benign	not provided		no assertion criteria provided	clinical testing