Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001203386 | SCV001374549 | pathogenic | Townes syndrome | 2019-07-31 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the SALL1 gene (p.Ser141Alafs*42). This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with clinical features of Townes-Brocks syndrome, including at least one individual where the variant was reported de novo (PMID: 9973281, Invitae). This variant is also known as c.419delC in the literature. 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. |