ClinVar Miner

Submissions for variant NM_002047.4(GARS1):c.1034A>G (p.Glu345Gly)

dbSNP: rs1554338641
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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 RCV000653955 SCV000775845 likely pathogenic Charcot-Marie-Tooth disease type 2 2020-01-07 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Glu345 amino acid residue in GARS. Other variant(s) that disrupt this residue have been observed in individuals with GARS-related conditions (PMID: 28708278), which suggests that this may be a clinically significant amino acid residue. 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. This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 543246). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 345 of the GARS protein (p.Glu345Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine.

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