ClinVar Miner

Submissions for variant NM_001174096.2(ZEB1):c.2522A>C (p.Gln841Pro)

gnomAD frequency: 0.00680  dbSNP: rs118020901
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000013469 SCV001138016 uncertain significance Corneal dystrophy, Fuchs endothelial, 6 2019-05-28 criteria provided, single submitter clinical testing
GeneDx RCV002225264 SCV002504023 likely benign not provided 2018-07-31 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Labcorp Genetics (formerly Invitae), Labcorp RCV002225264 SCV003254121 benign not provided 2023-12-19 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017235 SCV004848342 likely benign not specified 2024-04-18 criteria provided, single submitter clinical testing The p.Gln841Pro variant in ZEB1 is classified as likely benign because it has been identified in 3.5% (372/10606) of Finnish chromosomes, including 6 total homozygotes by gnomAD (http://gnomad.broadinstitute.org, v.4.0.0). ACMG/AMP Criteria applied: BS1.
OMIM RCV000013469 SCV000033716 pathogenic Corneal dystrophy, Fuchs endothelial, 6 2010-01-01 no assertion criteria provided literature only
Reproductive Health Research and Development, BGI Genomics RCV000013469 SCV001142409 uncertain significance Corneal dystrophy, Fuchs endothelial, 6 2020-01-06 no assertion criteria provided curation The ZEB1 gene is known as TCF8 in the published literature (PMID: 20036349). NM_030751.5:c.2519A>C in the ZEB1 gene has an allele frequency of 0.033 in European (Finnish) subpopulation in the gnomAD database. 22 homozygous occurrences are observed in the gnomAD database. Since the Fuchs Corneal Dystrophy was reported as Late-Onset, we determined to not apply the number of homozygousity as a strong benign evidence. Gupta et al reported an individual with fuchs endothelial corneal dystrophy harboing this variant (PMID: 26622166). In addition, Riazuddin et al. reported segregation of p.Q840P mutation in a large, multigenerational FCD pedigree, and concluded this allele to be sufficient but not necessary for pathogenesis. However, the author also stated that a second, independent genetic event might account for the phenotype in the other patients having not this variant (PMID: 20036349). We interpret it as variant of uncertain significance (VUS). ACMG/AMP criteria applied: BS1, PP4.

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