ClinVar Miner

Submissions for variant NM_002047.4(GARS1):c.999G>C (p.Glu333Asp)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003581439 SCV004295105 pathogenic Charcot-Marie-Tooth disease type 2 2023-03-26 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 GARS function (PMID: 29520015). 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) has been performed at Invitae 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 GARS protein function. This variant is also known as p.Glu279Asp. This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease and/or hereditary motor neuropathy (PMID: 26000875, 26392352). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 333 of the GARS protein (p.Glu333Asp).

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