ClinVar Miner

Submissions for variant NM_002047.4(GARS1):c.843G>A (p.Met281Ile) (rs545669679)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000992026 SCV001143987 likely benign not provided 2018-11-27 criteria provided, single submitter clinical testing
Invitae RCV001337244 SCV001530837 uncertain significance Charcot-Marie-Tooth disease, type 2 2020-09-11 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 281 of the GARS protein (p.Met281Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs545669679, ExAC 0.06%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with GARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 804828). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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.

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