Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018357 | SCV004848102 | pathogenic | Tuberous sclerosis syndrome | 2019-02-01 | criteria provided, single submitter | clinical testing | The p.Ser1539fs variant in TSC2 has not been previously reported in individuals with tuberous sclerosis or in large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1539 and leads to a premature termination codon 27 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the TSC2 gene is an established disease mechanism in individuals with tuberus sclerosis. In summary, this variant meets criteria to be classified as pathogenic for tuberous sclerosis in an autosomal dominant manner based upon the predicted impact to the protein and absence in controls. |