ClinVar Miner

Submissions for variant NM_001605.3(AARS1):c.1496T>G (p.Phe499Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003743113 SCV004454353 uncertain significance Charcot-Marie-Tooth disease type 2 2024-05-16 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 499 of the AARS protein (p.Phe499Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AARS-related conditions. 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 AARS 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.
Ambry Genetics RCV004371844 SCV004917105 uncertain significance Inborn genetic diseases 2024-01-09 criteria provided, single submitter clinical testing The c.1496T>G (p.F499C) alteration is located in exon 12 (coding exon 11) of the AARS gene. This alteration results from a T to G substitution at nucleotide position 1496, causing the phenylalanine (F) at amino acid position 499 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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