ClinVar Miner

Submissions for variant NM_000035.4(ALDOB):c.10C>T (p.Arg4Ter) (rs118204428)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000000500 SCV000220885 likely pathogenic Hereditary fructosuria 2014-11-13 criteria provided, single submitter literature only
Invitae RCV000000500 SCV001390518 pathogenic Hereditary fructosuria 2020-08-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg4*) in the ALDOB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs118204428, ExAC 0.006%). This variant has been observed to segregate with hereditary fructose intolerance in a family (PMID: 8071980). ClinVar contains an entry for this variant (Variation ID: 471). This variant is also known as R3op in the literature. Loss-of-function variants in ALDOB are known to be pathogenic (PMID: 18541450). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000000500 SCV001448499 pathogenic Hereditary fructosuria 2020-11-27 criteria provided, single submitter clinical testing Variant summary: ALDOB c.10C>T (p.Arg4X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251348 control chromosomes (gnomAD). c.10C>T (also known as R3op in the literature) has been observed to segregate with Hereditary Fructose Intolerance in 4 homozygous affected siblings from a large consanguineous family with a reported history of sugar intolerance in several family members (Ali_1994). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000000500 SCV000020649 pathogenic Hereditary fructosuria 1994-06-01 no assertion criteria provided literature only
ATS em Genética Clínica,Universidade Federal do Rio Grande do Sul RCV000000500 SCV001573828 likely pathogenic Hereditary fructosuria 2021-03-18 no assertion criteria provided literature only

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