ClinVar Miner

Submissions for variant NM_001130144.3(LTBP3):c.1645C>G (p.Pro549Ala)

gnomAD frequency: 0.00006  dbSNP: rs145060640
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001866048 SCV002119552 uncertain significance Brachyolmia-amelogenesis imperfecta syndrome 2023-12-02 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 549 of the LTBP3 protein (p.Pro549Ala). This variant is present in population databases (rs145060640, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LTBP3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1206357). 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 tolerated. 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.
Ambry Genetics RCV002405255 SCV002709259 uncertain significance Inborn genetic diseases 2022-10-17 criteria provided, single submitter clinical testing The p.P549A variant (also known as c.1645C>G), located in coding exon 11 of the LTBP3 gene, results from a C to G substitution at nucleotide position 1645. The proline at codon 549 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003426177 SCV004118320 uncertain significance LTBP3-related disorder 2023-01-25 criteria provided, single submitter clinical testing The LTBP3 c.1645C>G variant is predicted to result in the amino acid substitution p.Pro549Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.014% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-65318672-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001573933 SCV001800513 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001573933 SCV001967368 likely benign not provided no assertion criteria provided clinical testing

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.