Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
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. |
Prevention |
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, |
RCV001573933 | SCV001800513 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001573933 | SCV001967368 | likely benign | not provided | no assertion criteria provided | clinical testing |