Submissions for variant NM_004990.4(MARS1):c.2391A>C (p.Thr797=) (rs140573721)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000428931	SCV000532182	likely benign	not specified	2017-10-17	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000555547	SCV000655636	uncertain significance	Interstitial lung and liver disease; Charcot-Marie-Tooth disease, axonal, type 2u	2019-12-18	criteria provided, single submitter	clinical testing	This sequence change affects codon 797 of the MARS mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MARS protein. This variant is present in population databases (rs140573721, ExAC 0.1%). This variant has not been reported in the literature in individuals with MARS-related disease. ClinVar contains an entry for this variant (Variation ID: 389593). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, 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.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173652	SCV001336754	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing