ClinVar Miner

Submissions for variant NM_000361.3(THBD):c.683C>T (p.Pro228Leu)

gnomAD frequency: 0.00060  dbSNP: rs375011249
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
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 RCV000768336 SCV000899026 uncertain significance Atypical hemolytic-uremic syndrome with thrombomodulin anomaly; Thrombomodulin-related bleeding disorder 2021-03-30 criteria provided, single submitter clinical testing THBD NM_000361.2 exon 1 p.Pro228Leu (c.683C>T): This variant has not been reported in the literature but is present in 31/588344 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs375011249). Evolutionary conservation and computational predictive tools suggest that this variant may not 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 RCV001359451 SCV001555322 uncertain significance not provided 2023-10-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 228 of the THBD protein (p.Pro228Leu). This variant is present in population databases (rs375011249, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with THBD-related conditions. ClinVar contains an entry for this variant (Variation ID: 626184). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mayo Clinic Laboratories, Mayo Clinic RCV001359451 SCV004225473 uncertain significance not provided 2022-06-07 criteria provided, single submitter clinical testing BP4
Ambry Genetics RCV004027215 SCV004964890 uncertain significance Inborn genetic diseases 2021-09-16 criteria provided, single submitter clinical testing The c.683C>T (p.P228L) alteration is located in exon 1 (coding exon 1) of the THBD gene. This alteration results from a C to T substitution at nucleotide position 683, causing the proline (P) at amino acid position 228 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.