ClinVar Miner

Submissions for variant NM_003239.5(TGFB3):c.464G>A (p.Arg155Gln)

dbSNP: rs925224125
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002533512 SCV000826776 uncertain significance Rienhoff syndrome 2024-07-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 155 of the TGFB3 protein (p.Arg155Gln). This variant is present in population databases (no rsID available, gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Loeys-Dietz syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 575813). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TGFB3 protein function with a negative predictive value of 80%. This variant disrupts the p.Arg155 amino acid residue in TGFB3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31898322, 32897753; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001027806 SCV001190420 uncertain significance Arrhythmogenic right ventricular dysplasia 1; Rienhoff syndrome 2021-03-30 criteria provided, single submitter clinical testing TGFB3 NM_003239.4 exon 2 p.Arg155Gln (c.464G>A): This variant has not been reported in the literature but is present in 0.0003% (1/251366) of total alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/14-76437950-C-T). This variant is present in ClinVar (Variation ID:575813). 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.
GeneDx RCV001568251 SCV001792093 uncertain significance not provided 2020-10-20 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function

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