ClinVar Miner

Submissions for variant NM_000035.4(ALDOB):c.-11+1G>C (rs181639417)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000589599 SCV000693982 pathogenic Hereditary fructosuria 2016-02-12 criteria provided, single submitter clinical testing Variant summary: Variant affects a conserved nucleotide located at the donor splice site of the first exon. Mutation taster predicts the variant to be disease causing and 5/5 in silico tools predict the variant to result in the elimination of the splice donor site. The variant was found in the cohort of 1000G at a very low allele frequency (1/5008). It was also reported in HFI patients with potentially pathogenic ALDOB mutation in trans indicating pathogenicity. Furthermore, the variant was shown to result in aberrant splicing leading to complete retention of the first intron and consequently to the loss of ALDOB expression (Coffee_JIMD_2010). A reputable database classifies variant as pathogenic (without evidence to impenitently evaluate). Considering all evidence, the variant was classified as Pathogenic.
Invitae RCV000589599 SCV000937576 pathogenic Hereditary fructosuria 2018-11-05 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the ALDOB gene. It does not directly change the encoded amino acid sequence of the ALDOB protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another ALDOB variant in individuals affected with fructose intolerance (PMID: 20882353, Invitae) and in one of these individuals it has been observed on the opposite chromosome (in trans) from another pathogenic variant. This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as IVS1+1G>C in the literature. ClinVar contains an entry for this variant (Variation ID: 495347). Experimental studies have shown that this intronic change disrupts splicing and causes a loss of ALDOB activity (PMID: 20882353). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000589599 SCV000789240 likely pathogenic Hereditary fructosuria 2017-01-19 no assertion criteria provided clinical testing

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