ClinVar Miner

Submissions for variant NM_001605.3(AARS1):c.1546G>A (p.Val516Met)

dbSNP: rs143844046
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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 RCV001218745 SCV001390643 uncertain significance Charcot-Marie-Tooth disease type 2 2024-10-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 516 of the AARS protein (p.Val516Met). This variant is present in population databases (rs143844046, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 947633). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AARS protein function. 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.
Ambry Genetics RCV002462840 SCV002756125 uncertain significance Inborn genetic diseases 2022-01-31 criteria provided, single submitter clinical testing The p.V516M variant (also known as c.1546G>A), located in coding exon 11 of the AARS gene, results from a G to A substitution at nucleotide position 1546. The valine at codon 516 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004726987 SCV005332760 uncertain significance not provided 2024-01-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25817015)

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