Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV000208441 | SCV000264271 | uncertain significance | Brugada syndrome | 2015-05-21 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000029159 | SCV000290315 | likely benign | Progressive familial heart block type 1B | 2017-09-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000443394 | SCV000521223 | uncertain significance | not specified | 2016-10-17 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TRPM4 gene. Using linkage analysis, Liu et al. (2010) observed the A432T variant segregated with right-bundle branch block (RBBB) in at least 20 family members of a large kindred. Although one affected individual did not harbor the A432T variant, the authors concluded that this was a phenocopy based on the uniqueness of the RBBB compared to other affected family members (Liu et al., 2010). A432T was also observed in a Turkish man with incomplete RBBB who also harbored a second variant in the TRPM4 gene (Stallmeyer et al., 2012).The NHLBI Exome Sequencing Project reports A432T was observed in 9/8,600 (0.1%) alleles from individuals of European background, and it was also observed in 18/11,524 (0.15%) alleles from from individuals of Latino background in the Exome Aggregation Consortium (ExAC) data set, indicating it may be a rare benign variant in these populations. However, the A432T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Although functional studies have been discordant as to whether or not the A432T variant results in gain or loss of protein function, in silico analysis predicts this variant is probably damaging to the protein structure/function (Liu et al., 2010; Syam et al., 2016). |
| DNA and Cytogenetics Diagnostics Unit, |
RCV000029159 | SCV000745390 | uncertain significance | Progressive familial heart block type 1B | 2017-11-07 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000029159 | SCV000051804 | pathogenic | Progressive familial heart block type 1B | 2012-01-01 | no assertion criteria provided | literature only |