ClinVar Miner

Submissions for variant NM_001605.3(AARS1):c.2275G>A (p.Glu759Lys)

gnomAD frequency: 0.00020  dbSNP: rs137894161
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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 RCV000197440 SCV000254744 likely benign Charcot-Marie-Tooth disease type 2 2025-01-06 criteria provided, single submitter clinical testing
GeneDx RCV000235633 SCV000294146 uncertain significance not provided 2018-03-27 criteria provided, single submitter clinical testing The E759K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E759K variant was not observed at any significant frequency in approximately 6500 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 E759K 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 occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Ambry Genetics RCV002519573 SCV003704961 uncertain significance Inborn genetic diseases 2021-10-12 criteria provided, single submitter clinical testing The c.2275G>A (p.E759K) alteration is located in exon 16 (coding exon 15) of the AARS gene. This alteration results from a G to A substitution at nucleotide position 2275, causing the glutamic acid (E) at amino acid position 759 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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