ClinVar Miner

Submissions for variant NM_001605.3(AARS1):c.2738G>A (p.Gly913Asp)

gnomAD frequency: 0.00001  dbSNP: rs369774476
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235881 SCV000294195 uncertain significance not provided 2019-11-12 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28493438, 31791873)
Labcorp Genetics (formerly Invitae), Labcorp RCV000687989 SCV000815584 pathogenic Charcot-Marie-Tooth disease type 2 2023-09-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects AARS function (PMID: 28493438). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AARS protein function. ClinVar contains an entry for this variant (Variation ID: 246598). This missense change has been observed in individual(s) with autosomal recessive developmental and epileptic encephalopathy (PMID: 28493438, 31791873, 34446925). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant has been reported in individual(s) with autosomal dominant Charcot-Marie-Tooth disease (Invitae); however, the role of the variant in this condition is currently unclear. This variant is present in population databases (rs369774476, gnomAD 0.006%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 913 of the AARS protein (p.Gly913Asp).
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000995470 SCV001149655 pathogenic Developmental and epileptic encephalopathy, 29 2018-07-30 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000995470 SCV001439950 uncertain significance Developmental and epileptic encephalopathy, 29 2019-01-01 criteria provided, single submitter clinical testing This variant was identified as compound heterozygous.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000235881 SCV001446715 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
OMIM RCV000995470 SCV002051752 pathogenic Developmental and epileptic encephalopathy, 29 2022-03-02 no assertion criteria provided literature only

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