ClinVar Miner

Submissions for variant NM_002047.4(GARS1):c.1553A>G (p.Tyr518Cys)

gnomAD frequency: 0.00002  dbSNP: rs753947676
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001439803 SCV001642697 likely benign Charcot-Marie-Tooth disease type 2 2023-12-16 criteria provided, single submitter clinical testing
GeneDx RCV000863606 SCV001772666 likely benign not provided 2018-12-28 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000863606 SCV004235117 uncertain significance not provided 2023-11-07 criteria provided, single submitter clinical testing
GeneDx RCV000414190 SCV000491865 uncertain significance not specified 2016-11-11 flagged submission clinical testing A variant of uncertain significance has been identified in the GARS gene. The Y518C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Y518C 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. This substitution alters a position that is conserved in mammals and is predicted to be within the catalytic domain of the protein (He et al., 2015). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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