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

dbSNP: rs864309533

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000202634	SCV001226711	pathogenic	Hereditary fructosuria	2023-08-05	criteria provided, single submitter	clinical testing	This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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. Loss-of-function variants in ALDOB are known to be pathogenic (PMID: 18541450). This premature translational stop signal has been observed in individuals with hereditary fructose intolerance (PMID: 1967768, 15880727). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 218381). This variant is also known as L288delC.
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.
GeneDx	RCV003441781	SCV004167724	pathogenic	not provided	2023-10-19	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also known as L288deltaC; This variant is associated with the following publications: (PMID: 1967768, 31589614, 26677512, 15880727, 31591370, 36028839, 20848650)
Baylor Genetics	RCV000202634	SCV004196671	pathogenic	Hereditary fructosuria	2023-08-06	criteria provided, single submitter	clinical testing
GeneReviews	RCV000202634	SCV000257573	not provided	Hereditary fructosuria		no assertion 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
Natera, Inc.	RCV000202634	SCV002078711	pathogenic	Hereditary fructosuria	2021-01-04	no assertion criteria provided	clinical testing