ClinVar Miner

Submissions for variant NM_002047.4(GARS1):c.471G>C (p.Leu157Phe)

gnomAD frequency: 0.00001  dbSNP: rs367915362
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538443 SCV000657699 uncertain significance Charcot-Marie-Tooth disease type 2 2023-10-07 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 157 of the GARS protein (p.Leu157Phe). This variant is present in population databases (rs367915362, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with GARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 476758). 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. 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.
CeGaT Center for Human Genetics Tuebingen RCV000998783 SCV001155059 uncertain significance not provided 2017-10-01 criteria provided, single submitter clinical testing
GeneDx RCV000998783 SCV001816730 uncertain significance not provided 2020-10-01 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004024374 SCV003630018 uncertain significance not specified 2022-06-13 criteria provided, single submitter clinical testing The c.471G>C (p.L157F) alteration is located in exon 4 (coding exon 4) of the GARS gene. This alteration results from a G to C substitution at nucleotide position 471, causing the leucine (L) at amino acid position 157 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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