ClinVar Miner

Submissions for variant NM_000035.4(ALDOB):c.113-1_115del (rs786204598)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169352 SCV000220722 likely pathogenic Hereditary fructosuria 2014-09-23 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169352 SCV000918413 likely pathogenic Hereditary fructosuria 2021-02-06 criteria provided, single submitter clinical testing Variant summary: ALDOB c.113-1_115delGGTA is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 250930 control chromosomes. c.113-1_115delGGTA has been reported in the literature in at-least one homozygous individual affected with Hereditary Fructose Intolerance and subsequently cited by others (example, Cross_1990, Ali_1998, Kaiser_1991). These data indicate that the variant may 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 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV000169352 SCV001163211 pathogenic Hereditary fructosuria criteria provided, single submitter clinical testing
Invitae RCV000169352 SCV001225800 pathogenic Hereditary fructosuria 2020-02-14 criteria provided, single submitter clinical testing This variant is a deletion of the genomic region encompassing part of exon 3 (c.113-1_115del) of the ALDOB gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individuals affected with fructose intolerance (PMID: 2349937, 15880727). ClinVar contains an entry for this variant (Variation ID: 188974). Loss-of-function variants in ALDOB are known to be pathogenic (PMID: 18541450). For these reasons, this variant has been classified as Pathogenic.
ATS em Genética Clínica,Universidade Federal do Rio Grande do Sul RCV000169352 SCV001573863 likely pathogenic Hereditary fructosuria 2021-03-18 no assertion criteria provided literature only

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