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Gene Exon/Intron Mutation Mutation Type # Seen Comments
TSC1 Intron 03 327+15 A>G r-polym-prob 2 Pathogenicity uncertain
TSC1 Exon 04 342 C>A 41 L>I +2 r-polym 1 Conservative change. Seen in one family where it did not segregate with TSC.
TSC1 Exon 04 370 T>C 50 L>P -3 mis-prob 1 Pathogenicity uncertain, nonconservative change. No parental DNA. Pt had 2nd miss in TSC1 2641 T>C
TSC1 Exon 04 403 T>C 61 L>P -3 mis-conf 1 Non-conservative change. Not present in unaffected parents.
TSC1 Intron 04 432-1 G>A spl 3  
TSC1 Exon 05 471 G>A 84 A>T 0 r-polym 1 Unaffected parent same base change
TSC1 Exon 05 492-493 del TC 91S-FS-X @ 105 delFS 1  
TSC1 Exon 05 499 T>G 93 L>R -2 mis-prob 1 Pathogenicity uncertain, nonconservative change. No parental DNA.
TSC1 Exon 05 583 A>G 121 K>R +2 spl-prob 1 Affects 2nd to last base of exon. No parental DNA.
TSC1 Intron 05 584+1 G>T spl 1  
TSC1 Intron 05 584+5 G>A spl-prob 1 Pathogenicity uncertain. 1 parent screened neg
TSC1 Exon 06 666 C>T 149Q>X non 1  
TSC1 Exon 07 741 G>T 174 E>X non 1  
TSC1 Exon 07 776 C>T 185Y silent r-polym 1  
TSC1 Exon 07 790 G>C 190 R>P -2 mis-prob 1 Pathogenicity uncertain, nonconservative change. No parental DNA.
TSC1 Exon 07 868-869 del TT 216 F>X delFS 1  
TSC1 Intron 7 884+7 T>A r-polym 1 Unaffected parent same base change
TSC1 Intron 7 884+38 ins C r-polym 1  
TSC1 Intron 07 885-15 A>G r-polym-prob 1 Pathogenicity uncertain. No parental DNA
TSC1 Exon 08 903 C>T 228 R>X non 1  
TSC1 Exon 08 915 G>T 232 E>X non 1  
TSC1 Exon 08 954 C>T 245 R>X non 8  
TSC1 Exon 08 958 G>AŻ 246 R>K +2 spl-prob 2 Affects last base of exon
TSC1 Exon 08 958 G>C 246 R>T -1 mis-spl-prob 2 Affects last base of exon
TSC1 Exon 09 970 ins T 250L-FS-X @ 254 insFS 1  
TSC1 Exon 09 1034 T>A 271 Y>X non 1  
TSC1 Exon 09 1046 T>G 275 Y>X non 1  
TSC1 Exon 09 1055-1056 del TC 278S-FS-X @ 298 delFS 1  
TSC1 Exon 09 1122 C>T 301 Q>X non 1  
TSC1 Exon 09 1122-1134+1 del 14 CAGAATAGCTATGG delFS 1  
TSC1 Exon 09 1133-1134+5 del 7 TGGTAAA delFS 1 Deletion through splice site
TSC1 Exon 09 1134 G>A 305 G>R -2 mis-spl-prob 1 Affects last base of exon
TSC1 Exon 10 1186T>C 322 M>T -1 polym 15%  
TSC1 Exon 10 1209-1210 del CT 330L-FS-X @339 delFS 2  
TSC1 Exon 10 1210 ins T 330L-FS-X @ 340 insFS 2  
TSC1 Exon 10 1227 C>T 336 R>W -3 r-polym-prob 1 Pt had other mutation found
TSC1 Exon 11 1261 G>A 347 W>X non 1  
TSC1 Exon 11 1268 A>G 349P silent r-polym 1  
TSC1 Exon 11 1300C>A 360 T>N 0 r-polym-prob 1 Pt had other mutation found
TSC1 Exon 11 1313-1326 del 14 TGTCCCACCTGATC 364N-FS-X @ 370 delFS 1  
TSC1 Exon 11 1326 C>T 369L silent r-polym 1  
TSC1 Exon 11 1334-1335 ins AC 371H-FS-X @ 440 insFS 1  
TSC1 Intron 11 1363-33 A>G polym 16%  
TSC1 Exon 12 1429 C>T 403 S>L -2 r-polym-prob 1 Pt had other mutation found
TSC1 Exon 12 1478 del C 419P-FS-X @ 439 delFS 1  
TSC1 Exon 13 1524 C>T 435 Q>X non 1  
TSC1 Exon 14 1556 A>G 445E silent polym 6%  
TSC1 Exon 14 1559 del G 446E-FS-X @ 456 delFS 1  
TSC1 Exon 14 1652-1655 del AGAA 477K-FS-X @ 530 delFS 1  
TSC1 Intron 14 1658-37 C>T polym 9%  
TSC1 Intron 14 1659+6 G>A r-polym-prob 1 Pathogenicity uncertain. No definite mutation found in pt
TSC1 Intron 14 1660-2 A>G spl 1  
TSC1 Exon 15 1703 ins C 494A-FS-X @ 504 insFS 1  
TSC1 Exon 15 1719 C>T 500 R>X non 1  
TSC1 Exon 15 1736 ins T 505S-FS-X @ 534 insFS 1  
TSC1 Exon 15 1746 C>T 509 R>X non 4  
TSC1 Exon 15 1780 del A 520H-FS-X @ 531 delFS 1  
TSC1 Exon 15 1890 C>T 557L silent r-polym 1  
TSC1 Exon 15 1916 del C 565P-FS-X @ 628 delFS 1  
TSC1 Exon 15 1929-1930 del AG 570R-FS-X @ 570 delFS 2  
TSC1 Exon 15 1948-1963 16bpdel TGGAGACCAGTATCTT 576L-FS-X @ 623 delFS 1  
TSC1 Exon 15 1950 G>T 577 E>X non 1  
TSC1 Exon 15 1981 A>G 587 K>R +2 r-polym 5 Seen in unaffected samples
TSC1 Exon 15 1982 A>G 587K silent r-polym 1  
TSC1 Exon 15 2060 del A 613P-FS-X @ 628 delFS 1  
TSC1 Exon 15 2072 del T 617H-FS-X @ 628 delFS 1  
TSC1 Exon 15 2075 del T 618H-FS-X @ 628 delFS 1  
TSC1 Exon 15 2105-2108 del AAAG 628L-FS-X @ 651 delFS 5  
TSC1 Exon 15 2122-2123 del AC 634N-FS-X @ 686 delFS 1  
TSC1 Exon 15 2163 del G 648-FS-X @ 652 delFS 1  
TSC1 Exon 15 2180 ins A 653I-FS-X @ 687 insFS 2  
TSC1 Exon 15 2181 C>T 654 Q>X non 1  
TSC1 Exon 15 2195 C>G 658 D>E +2 r-polym-prob 1 Pathogenicity uncertain conservative change
TSC1 Exon 15 2197 C>T 659 A>V 0 r-polym-prob 1 Pathogenicity uncertain conservative change
TSC1 Intron 15 2218+1 G>A spl 1  
TSC1 Exon 16 2243 C>T 674V silent r-polym 1  
TSC1 Intron 16 2263-5 A>G spl-poss 1 Pathogenicity uncertain
TSC1 Exon 17 2295 C>T 629 R>X non 4  
TSC1 Exon 17 2326-2330 ins TAGTT 702L-FS-X @ 725 insFS 1  
TSC1 Exon 17 2333 T>A 704 Y>X non 1  
TSC1 Exon 17 2352 C>T 711 Q>X non 1  
TSC1 Exon 17 2355-2359 del CATCG 712H-FS-X @ 731 delFS 1  
TSC1 Exon 17 2365 del G 715R-FS-X @ 723 delFS 1 mosaic
TSC1 Exon 17 2394-2397 del AAAG 725K-FS-X @ 735 delFS 1  
TSC1 Exon 17 2398 C>A 726 A>E -1 r-polym 1 Reported benign variant
TSC1 Exon 17 2415 C>T 732 H>Y +2 polym 10, 1.2% Reported benign variant
TSC1 Exon 18 2448 C>T 743 Q>X non 2  
TSC1 Exon 18 2471 G>A 750 W>X non 1  
TSC1 Exon 18 2481 C>T 754L silent r-polym 1  
TSC1 Exon 18 2500-2515del16 GATACAATCAGCTCCA 760R-FS-X @ 767 delFS 1  
TSC1 Exon 18 2512 del T 764L-FS-X @ 772 delFS 1  
TSC1 Exon 18 2514 C>T 765 Q>X non 1  
TSC1 Exon 18 2520 C>T 767 Q>X non 1  
TSC1 Exon 18 2562 C>T 781 Q>X non 1  
TSC1 Exon 18 2577 C>T 786 R>X non 2  
TSC1 Intron 18 2613-35 T>C spl-prob 1 Reported as definite mutation: Human Mutation 1999 14:401-411
TSC1 Exon 19 2641 T>C 807 I>T -1 mis-poss 1 Pathogenicity uncertain, nonconservative change. No parental DNA. Pt had 2nd miss in TSC1 370 T>C
TSC1 Exon 19 2690 ins G insFS 1  
TSC1 Exon 19 2692-2693 del CT 824T-FS-X @ 838 delFS 1  
TSC1 Exon 19 2718 C>T 833 Q>X non 1  
TSC1 Exon 19 2719 ins A 833-FS-X @ 839 insFS 1  
TSC1 Intron 19 2724-21 T>C r-polym-prob 1  
TSC1 Exon 20 2729-2108 del AAAC 836S-FS-X @ 847 delFS 1  
TSC1 Exon 20 2787 ins G 856G-FS-X @ 903 insFS 1  
TSC1 Exon 21 2867 C>T 882A silent r-polym 6  
TSC1 Exon 21 2937 C>T 906 Q>X non 1  
TSC1 Exon 21 3005-3006 del AT 928K-FS-X @ 948 delFS 1  
TSC1 Intron 21 3034 +51 A>G r-polym 1  
TSC1 Exon 22 3050 C>T 943A silent polym 6%  
TSC1 Intron 22 3197-43 G>C r-polym 4  
TSC1 Intron 22 3197-54 G>A r-polym 2  
TSC1 Exon 23 3503 G>A 1094E silent r-polym 1  
TSC1 Exon 23 3545 C>T 1108G silent r-polym 2  

Key to abbreviations used in tables

Abbreviation 

Definition
delFS frameshift deletion
spl splice
r-polym rare polymorphism
r-polym-prob rare polymorphism probable
insFS frameshift insertion
non nonsense
mis-conf confirmed missense by parental checks
mis-poss missense possible
mis-spl-conf missense splice confirmed mutation
mis-prob missense probable, nonconservative change and 0/1 parental check
infrdel-conf inframe deletion confirmed by parental checks
# seen # times seen as heterozygous
# seen % % of heterozygous alleles

Key to amino acid substitution scoring

BLOSUM-62 scoring matrix for amino acid substitutions

From Henikoff and Henikoff. PNAS 89:10915-9, 1992.

The more negative the number, the less conservative the change

 

  A C D E F G H I K L M N P Q R S T V W Y  
A 4 0 -2 -1 -2 0 -2 -1 -1 -1 -1 -2 -1 -1 -1 1 0 0 -3 -2 A
C 0 9 -3 -4 -2 -3 -3 -1 -3 -1 -1 -3 -3 -3 -3 -1 -1 -1 -2 -2 C
D -2 -3 6 2 -3 -1 -1 -3 -1 -4 -3 1 -1 0 -2 0 -1 -3 -4 -3 D
E -1 -4 2 5 -3 -2 0 -3 1 -3 -2 0 -1 2 0 0 -1 -2 -3 -2 E
F -2 -2 -3 -3 6 -3 -1 0 -3 0 0 -3 -4 -3 -3 -2 -2 -1 1 3 F
G 0 -3 -1 -2 -3 6 -2 -4 -2 -4 -3 0 -2 -2 -2 0 -2 -3 -2 -3 G
H -2 -3 -1 0 -1 -2 8 -3 -1 -3 -2 1 -2 0 0 -1 -2 -3 -2 2 H
I -1 -1 -3 -3 0 -4 -3 4 -3 2 1 -3 -3 -3 -3 -2 -1 3 -3 -1 I
K -1 -3 -1 1 -3 -2 -1 -3 5 -2 -1 0 -1 1 2 0 -1 -2 -3 -2 K
L -1 -1 -4 -3 0 -4 -3 2 -2 4 2 -3 -3 -2 -2 -2 -1 1 -2 -1 L
M -1 -1 -3 -2 0 -3 -2 1 -1 2 5 -2 -2 0 -1 -1 -1 1 -1 -1 M
N -2 -3 1 0 -3 0 1 -3 0 -3 -2 6 -2 0 0 1 0 -3 -4 -2 N
P -1 -3 -1 -1 -4 -2 -2 -3 -1 -3 -2 -2 7 -1 -2 -1 -1 -2 -4 -3 P
Q -1 -3 0 2 -3 -2 0 -3 1 -2 0 0 -1 5 1 0 -1 -2 -2 -1 Q
R -1 -3 -2 0 -3 -2 0 -3 2 -2 -1 0 -2 1 5 -1 -1 -3 -3 -2 R
S 1 -1 0 0 -2 0 -1 -2 0 -2 -1 1 -1 0 -1 4 1 -2 -3 -2 S
T 0 -1 -1 -1 -2 -2 -2 -1 -1 -1 -1 0 -1 -1 -1 1 5 0 -2 -2 T
V 0 -1 -3 -2 -1 -3 -3 -3 -2 1 1 -3 -2 -2 -3 -2 0 4 -3 -1 V
W -3 -2 -4 -3 1 -2 -2 -3 -3 -2 -1 -4 -4 -2 -3 -3 -2 -3 11 2 W
Y -2 -2 -3 -2 3 -3 2 -1 -2 -1 -1 -2 -3 -1 -2 -2 -2 -1 2 7 Y
  A C D E F G H I K L M N P Q R S T V W Y