Tuberous Sclerosis Project Home Page

Mutation identification by Yew-Sing Choy, Ronald Perez, Sandra Dabora, Penelope S. Roberts, David Kwiatkowski

We have screened over 800 Tuberous Sclerosis (TSC) patients for mutations by dHPLC, quantitative PCR and long-range PCR. The entire coding sequence for the TSC2 gene was screened in all of the patients. Screening for mutations in TSC1, and examination for large rearrangements in TSC2 by quantitative PCR and long-range PCR was performed in those patients not found to have a small mutation in TSC2.

TSC1 database -- TSC1 has two non-coding exons preceding exon 3 which contains the initiator methionine ATG. The total 5' untranslated region is 221 bp, so that the A of the ATG can be numbered as either 1 or 222. We use the A=222 numbering system.

TSC2 database -- For TSC2 there are several possible numbering systems that are in use. We number from the first base of the initiator ATG coding. We also include all of the alternatively spliced exons in our numbering system for exons, so that there are 41 exons total, counting the ATG containing exon as exon 1.

Abbreviation

Definition

delFS

deletion resulting in a frameshift

insFS

insertion resulting in a frameshift

infrdel-conf

in-frame deletion confirmed as pathogenic by parental check

mis-conf

missense mutation confirmed as pathogenic by parental check

mis-poss

missense mutation, possible

mis-prob

missense mutation, probable; denotes a nonconservative amino acid substitution; parental check not possible.

mis-spl-conf

mutation that causes a missense change in amino acid, and may also affect splicing; confirmed by parental check

non

nonsense mutation

r-polym

rare polymorphism

r-polym-prob

rare polymorphism probable

spl

splice mutation

# seen

# times seen as heterozygote

# seen %

% indicates heterozygote frequency