Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001218743 | SCV001390641 | pathogenic | Townes syndrome | 2019-06-19 | criteria provided, single submitter | clinical testing | Truncating variants in the SALL1 gene are known to cause Townes-Brocks syndrome by haploinsufficiency (PMID: 16429401, 22308078) or by a dominant negative mechanism (PMID: 29395072). Truncations both upstream (p.Thr105Glnfs*78) and downstream (p.Arg260*) of this variant have been shown to be clinically significant and are consistent with a dominant negative mechanism (PMID: 17221874, 16088922, Invitae). This suggests that deletion of this region of the SALL1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. This sequence change results in a premature translational stop signal in the SALL1 gene (p.Arg251Serfs*19). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SALL1-related conditions. |