Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193147 | SCV001361815 | likely pathogenic | Holt-Oram syndrome | 2019-02-11 | criteria provided, single submitter | clinical testing | Variant summary: TBX5 c.192G>A (p.Trp64X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 246266 control chromosomes (gnomAD). A different variant leading to the same protein level change (c.191G>A (p.Trp64X)) has been reported in the literature in an individual affected with Holt-Oram Syndrome (Fan 2003; of note, while the authors described this variant as c.192G>A, their sequence data confirms that it was c.191G>A). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Institute of Medical Genetics and Applied Genomics, |
RCV001268738 | SCV001447884 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing |