ClinVar Miner

Submissions for variant NM_001605.3(AARS1):c.1604A>G (p.Tyr535Cys)

gnomAD frequency: 0.00001  dbSNP: rs756650948
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001346012 SCV001540173 uncertain significance Charcot-Marie-Tooth disease type 2 2020-12-21 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 535 of the AARS protein (p.Tyr535Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs756650948, ExAC 0.001%). This variant has not been reported in the literature in individuals with AARS-related conditions. 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. 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.
Revvity Omics, Revvity RCV003136010 SCV003821896 uncertain significance not provided 2022-10-12 criteria provided, single submitter clinical testing
GeneDx RCV003136010 SCV005080222 uncertain significance not provided 2023-12-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; 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: 25817015)

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