ClinVar Miner

Submissions for variant NM_000035.4(ALDOB):c.356_359CAAA[1] (p.Asn120fs) (rs387906225)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169213 SCV000220471 likely pathogenic Hereditary fructosuria 2014-07-02 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723843 SCV000229997 pathogenic not provided 2017-08-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000169213 SCV000916437 pathogenic Hereditary fructosuria 2018-03-20 criteria provided, single submitter clinical testing Variant summary: ALDOB c.360_363delCAAA (p.Asn120LysfsX32) 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 4.7e-05 in 277096 control chromosomes. This frequency is not higher than expected for a pathogenic variant in ALDOB causing Hereditary Fructose Intolerance (4.7e-05 vs 0.0045), allowing no conclusion about variant significance. The c.360_363delCAAA variant has been reported in the literature in multiple individuals affected with Hereditary Fructose Intolerance, both as a homozygous and compound heterozygous allele. 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. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000169213 SCV000948983 pathogenic Hereditary fructosuria 2018-11-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn120Lysfs*32) in the ALDOB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs762198323, ExAC 0.01%). This variant has been observed in combination with another ALDOB variant in individuals affected with fructose intolerance (PMID: 2339710, 26937407). ClinVar contains an entry for this variant (Variation ID: 188861). Loss-of-function variants in ALDOB are known to be pathogenic (PMID: 18541450). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000169213 SCV000020645 pathogenic Hereditary fructosuria 1990-06-01 no assertion criteria provided literature only
HFI Laboratory at Boston University,Boston University RCV000169213 SCV000067376 pathogenic Hereditary fructosuria no assertion criteria provided clinical testing
GeneReviews RCV000169213 SCV000257570 pathogenic Hereditary fructosuria 2015-10-07 no assertion criteria provided literature only

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