Submissions for variant NM_001605.3(AARS1):c.736C>T (p.Arg246Ter)

dbSNP: rs756337758

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001216699	SCV001388509	pathogenic	Charcot-Marie-Tooth disease type 2	2024-08-12	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg246*) in the AARS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AARS are known to be pathogenic (PMID: 25817015, 28493438, 34446925). This variant is present in population databases (rs756337758, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with AARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 945940). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001587235	SCV001814207	likely pathogenic	not provided	2021-08-31	criteria provided, single submitter	clinical testing	Identified as a germline variant in individuals with papillary thyroid carcinoma from a single family in the published literature (Wang et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27535533, 30957677)
Clinical Genetics, Academic Medical Center	RCV001587235	SCV001923977	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001587235	SCV001957057	uncertain significance	not provided		no assertion criteria provided	clinical testing