Submissions for variant NM_000035.4(ALDOB):c.360_363del (p.Asn120fs)

dbSNP: rs387906225

Total submissions: 15

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
Eurofins Ntd Llc (ga)	RCV000723843	SCV000229997	pathogenic	not provided	2017-08-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	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	2024-01-02	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. Loss-of-function variants in ALDOB are known to be pathogenic (PMID: 18541450). This variant is present in population databases (rs762198323, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with fructose intolerance (PMID: 2339710, 26937407). ClinVar contains an entry for this variant (Variation ID: 188861). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000169213	SCV001163209	pathogenic	Hereditary fructosuria		criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000169213	SCV002024882	pathogenic	Hereditary fructosuria	2022-02-04	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000723843	SCV002525799	pathogenic	not provided	2021-12-01	criteria provided, single submitter	clinical testing	PM2, PVS1
Fulgent Genetics, Fulgent Genetics	RCV000169213	SCV002811086	pathogenic	Hereditary fructosuria	2022-01-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002517627	SCV003543446	pathogenic	Inborn genetic diseases	2022-01-26	criteria provided, single submitter	clinical testing	The c.360_363delCAAA (p.N120Kfs*32) alteration, located in exon 4 (coding exon 3) of the ALDOB gene, consists of a deletion of 4 nucleotides from position 360 to 363, causing a translational frameshift with a predicted alternate stop codon after 32 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, this alteration has an overall frequency of <0.01% (14/282762) total alleles studied. The highest observed frequency was 0.02% (3/19954) of East Asian alleles. This alteration has been reported in multiple unrelated patients with hereditary fructose intolerance (Dazzo, 1990; Valadares, 2015; Kim, 2021). Based on the available evidence, this alteration is classified as pathogenic.
GeneDx	RCV000723843	SCV003936407	pathogenic	not provided	2023-06-30	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; This variant is associated with the following publications: (PMID: 34524712, 31980526, 33028743, 31589614, 34426522, 34162028, 15880727, 16406649, 23430936, 22975760, 2339710, 30202406, 26937407)
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	not provided	Hereditary fructosuria		no assertion provided	literature only	One of the six most common HFI variants in US and European populations including Turkey, Spain, Central Europe, France, US, and Italy
Natera, Inc.	RCV000169213	SCV001462844	pathogenic	Hereditary fructosuria	2020-09-16	no assertion criteria provided	clinical testing
ATS em Genética Clínica, Universidade Federal do Rio Grande do Sul	RCV000169213	SCV001573867	pathogenic	Hereditary fructosuria	2021-03-18	no assertion criteria provided	literature only