ClinVar Miner

Submissions for variant NM_000035.4(ALDOB):c.865del (p.Leu289fs) (rs864309533)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000202634 SCV001226711 pathogenic Hereditary fructosuria 2019-11-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu289Phefs*10) in the ALDOB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hereditary fructose intolerance (PMID: 1967768, 15880727). This variant is also known as L288delC in the literature ClinVar contains an entry for this variant (Variation ID: 218381). 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 RCV000202634 SCV001426780 pathogenic Hereditary fructosuria 2020-07-08 criteria provided, single submitter clinical testing Variant summary: ALDOB c.865delC (p.Leu289PhefsX10) 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. The variant allele was found at a frequency of 4e-06 in 251092 control chromosomes (gnomAD). The variant, c.865delC (also known as L288delC), has been reported in the literature in homozygous or compound heterozygous state in multiple individuals affected with Hereditary Fructose Intolerance (Cross_1990, Santer_2005, Esposito_2010, DiDato_2019). 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. Three submitters have provided clinical-significance assessments for this variant in ClinVar after 2014, and all of them classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneReviews RCV000202634 SCV000257573 pathogenic Hereditary fructosuria 2015-10-07 no assertion criteria provided literature only
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000202634 SCV000599823 pathogenic Hereditary fructosuria 2017-04-20 no assertion criteria provided clinical testing
ATS em Genética Clínica,Universidade Federal do Rio Grande do Sul RCV000202634 SCV001573872 likely pathogenic Hereditary fructosuria 2021-03-18 no assertion criteria provided literature only

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