ClinVar Miner

Submissions for variant NM_000035.4(ALDOB):c.178C>T (p.Arg60Ter) (rs118204429)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000000501 SCV000220395 likely pathogenic Hereditary fructosuria 2014-06-10 criteria provided, single submitter literature only
GeneDx RCV000760464 SCV000890352 pathogenic not provided 2018-07-25 criteria provided, single submitter clinical testing The R60X variant in the ALDOB gene has been reported previously in association with hereditary fructose intolerance, when present in the homozygous state or when in trans with another disease-causing variant (Ali et al., 1994; Santer et al., 2005; Davit-Spraul et al., 2008; Valadares et al., 2015). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R60X variant is observed in 20/277036 (0.007%) alleles in large population cohorts and no individuals were reported to be homozygous (Lek et al., 2016). We interpret R60X as a pathogenic variant.
Fulgent Genetics,Fulgent Genetics RCV000000501 SCV000894462 likely pathogenic Hereditary fructosuria 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000000501 SCV000916436 pathogenic Hereditary fructosuria 2017-11-09 criteria provided, single submitter clinical testing Variant summary: The ALDOB c.178C>T (p.Arg60X) variant results in a premature termination codon, predicted to cause a truncated or absent ALDOB protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 20/277036 control chromosomes (gnomAD) at a frequency of 0.0000722, which does not exceed the estimated maximal expected allele frequency of a pathogenic ALDOB variant (0.0044721). Multiple publications have cited the variant in affected compound heterozygote and homozygote patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000000501 SCV000964566 pathogenic Hereditary fructosuria 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg60*) in the ALDOB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs118204429, ExAC 0.02%). This variant has been observed to segregate with hereditary fructose intolerance in a family (PMID: 8071980) and has been reported in individuals affected with hereditary fructose intolerance (PMID: 8299883, 26937407, 8071980, 15880727, 20882353). ClinVar contains an entry for this variant (Variation ID: 472). Experimental studies have shown that this nonsense change produces an ALDOB protein that has null enzyme activity (PMID: 8299883). Loss-of-function variants in ALDOB are known to be pathogenic (PMID: 18541450). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000501 SCV000020650 pathogenic Hereditary fructosuria 1994-06-01 no assertion criteria provided literature only
GeneReviews RCV000000501 SCV000257568 pathogenic Hereditary fructosuria 2015-10-07 no assertion criteria provided literature only

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