ClinVar Miner

Submissions for variant NM_002047.4(GARS1):c.794C>T (p.Ser265Phe) (rs1554337974)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000533118 SCV000657704 likely pathogenic Charcot-Marie-Tooth disease, type 2 2017-04-21 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 265 of the GARS protein (p.Ser265Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with disease in a family affected with distal hereditary motor neuropathy type V (PMID: 23279345) and a family affected with distal motor neuropathy (Invitae). This variant is also known as p.Ser211Phe in the literature. Experimental studies have shown that this missense change severely impairs charging of amino acids to tRNA (< 1% of wild type) (PMID: 25168514). In summary, this variant is a rare missense change that disrupts protein function and segregates with disease in two families. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000734019 SCV000862130 likely pathogenic not provided 2018-07-18 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789776 SCV000929160 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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