The relationship between CTH and Cystathioninuria (Autosomal Recessive) was evaluated using the ClinGen Clinical Validity Framework as of 04/17/19. Variants in CTH were first reported in humans with this disease as early as 2003 (Wang et al, PMID: 12574942). At least 6 unique variants and one large deletion have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 11 probands in 3 publications (PMIDs: 20584029, 19428278, 12574942). This gene-disease association is supported by a mouse model of Cystathioninuria. The biochemical function of cystathionine gamma-lyase, which is the enzyme responsible for catalyzing the cystathionine to cysteine reaction, is also supportive of a role in the disease. In summary, CTH is definitively associated with Cystathioninuria (Autosomal Recessive). This has been repeatedly demonstrated in both the functional research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Aminoacidopathy Gene Curation Expert Panel on 6/14/19 (SOP Version 6).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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