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

dbSNP: rs370793608

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000779689	SCV000916438	pathogenic	Hereditary fructosuria	2018-05-25	criteria provided, single submitter	clinical testing	Variant summary: ALDOB c.612T>G (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 250130 control chromosomes (gnomAD and publications). The variant, c.612T>G, has been reported in the literature in individuals affected with Hereditary Fructose Intolerance (Santer_2005, Gruchota_2006, Ferri_2012). 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. EGL Genetics classified this variant as pathogenic. The c.612T>A variant, causing the same codon change Y204X, has been reported in multiple affected individuals and classified as pathogenic/likely pathogenic by multiple clinical labs via ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000779689	SCV002231797	pathogenic	Hereditary fructosuria	2023-03-18	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 632627). This premature translational stop signal has been observed in individual(s) with hereditary fructose intolerance (PMID: 15880727). 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	RCV000779689	SCV004196704	pathogenic	Hereditary fructosuria	2023-05-30	criteria provided, single submitter	clinical testing
ATS em Genética Clínica, Universidade Federal do Rio Grande do Sul	RCV000779689	SCV001573845	likely pathogenic	Hereditary fructosuria	2021-03-18	no assertion criteria provided	literature only
GeneReviews	RCV000779689	SCV002029088	not provided	Hereditary fructosuria		no assertion provided	literature only