ClinVar Miner

Submissions for variant NM_003680.3(YARS1):c.122G>A (p.Gly41Glu) (rs1569778143)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000823816 SCV000964686 uncertain significance Charcot-Marie-Tooth disease, dominant intermediate C 2018-08-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 41 of the YARS protein (p.Gly41Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with YARS-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Variants that disrupt the p.Gly41 amino acid residue in YARS have been observed in affected individuals (PMID: 16429158). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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.

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