ClinVar Miner

Submissions for variant NM_002047.4(GARS1):c.1454C>T (p.Pro485Leu)

gnomAD frequency: 0.00001  dbSNP: rs1159290036
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001248093 SCV001421558 uncertain significance Charcot-Marie-Tooth disease type 2 2019-10-17 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GARS-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 485 of the GARS protein (p.Pro485Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine.
Ambry Genetics RCV004034918 SCV002756276 uncertain significance not specified 2022-07-16 criteria provided, single submitter clinical testing The p.P485L variant (also known as c.1454C>T), located in coding exon 11 of the GARS gene, results from a C to T substitution at nucleotide position 1454. The proline at codon 485 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Human Genetics Bochum, Ruhr University Bochum RCV003886494 SCV004704529 uncertain significance Charcot-Marie-Tooth disease type 2D 2023-09-18 criteria provided, single submitter clinical testing ACMG criteria used to clasify this variant: PP2, PP3

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