Submissions for variant NM_000035.4(ALDOB):c.612T>A (p.Tyr204Ter)

gnomAD frequency: 0.00001  dbSNP: rs370793608

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169110	SCV000220310	likely pathogenic	Hereditary fructosuria	2014-05-12	criteria provided, single submitter	literature only
Eurofins Ntd Llc (ga)	RCV000723842	SCV000231461	pathogenic	not provided	2014-06-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000169110	SCV001361106	pathogenic	Hereditary fructosuria	2019-09-09	criteria provided, single submitter	clinical testing	Variant summary: ALDOB c.612T>A (p.Tyr204X) 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 was absent in 251356 control chromosomes (gnomAD). c.612T>A has been reported in the literature in multiple individuals affected with Hereditary Fructose Intolerance (e.g. Ali_1993, Esposito_2010). These data indicate that the variant is very likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae	RCV000169110	SCV001405976	pathogenic	Hereditary fructosuria	2023-01-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 188782). This variant is also known as Y203X. This premature translational stop signal has been observed in individual(s) with hereditary fructose intolerance (PMID: 8438046). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr204*) 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).
Baylor Genetics	RCV000169110	SCV004196604	pathogenic	Hereditary fructosuria	2023-09-10	criteria provided, single submitter	clinical testing
ATS em Genética Clínica, Universidade Federal do Rio Grande do Sul	RCV000169110	SCV001573844	likely pathogenic	Hereditary fructosuria	2021-03-18	no assertion criteria provided	literature only
Natera, Inc.	RCV000169110	SCV002078716	pathogenic	Hereditary fructosuria	2021-01-13	no assertion criteria provided	clinical testing