ClinVar Miner

Submissions for variant NM_014324.6(AMACR):c.722A>G (p.Tyr241Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002676482 SCV002984886 uncertain significance Alpha-methylacyl-CoA racemase deficiency 2022-04-21 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 241 of the AMACR protein (p.Tyr241Cys). This variant is present in population databases (rs201659164, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with AMACR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003331385 SCV004037831 uncertain significance not specified 2023-08-31 criteria provided, single submitter clinical testing Variant summary: AMACR c.722A>G (p.Tyr241Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249816 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.722A>G in individuals affected with AMACR-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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