ClinVar Miner

Submissions for variant NM_001061.7(TBXAS1):c.1417G>T (p.Gly473Trp)

gnomAD frequency: 0.00006  dbSNP: rs149988492
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768333 SCV000899014 likely pathogenic Ghosal hematodiaphyseal dysplasia; Thromboxane synthetase deficiency 2017-12-12 criteria provided, single submitter clinical testing TBXAS1 NM_001061.4 exon 12 p.Gly474Trp (c.1420G>T): This variant has not been reported in the literature but is present in 9/34410 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs149988492). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001855972 SCV002128834 likely pathogenic not provided 2023-12-07 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 474 of the TBXAS1 protein (p.Gly474Trp). This variant is present in population databases (rs149988492, gnomAD 0.03%). This missense change has been observed in individual(s) with Ghosal hematodiaphyseal dysplasia (PMID: 33595912). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 626181). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Mendelics RCV002249469 SCV002516066 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001855972 SCV005409384 uncertain significance not provided 2024-01-04 criteria provided, single submitter clinical testing PP3, PM1_supporting, PM3_supporting

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