Incidental Mutation 'R1440:Tsc2'
ID 160971
Institutional Source Beutler Lab
Gene Symbol Tsc2
Ensembl Gene ENSMUSG00000002496
Gene Name TSC complex subunit 2
Synonyms tuberin, Nafld, tuberous sclerosis 2
MMRRC Submission 039495-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1440 (G1)
Quality Score 151
Status Validated
Chromosome 17
Chromosomal Location 24814790-24851604 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 24833366 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 686 (Y686C)
Ref Sequence ENSEMBL: ENSMUSP00000154338 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000097373] [ENSMUST00000226284] [ENSMUST00000226398] [ENSMUST00000227607] [ENSMUST00000227745] [ENSMUST00000228412]
AlphaFold no structure available at present
Predicted Effect possibly damaging
Transcript: ENSMUST00000097373
AA Change: Y686C

PolyPhen 2 Score 0.907 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000094986
Gene: ENSMUSG00000002496
AA Change: Y686C

DomainStartEndE-ValueType
Pfam:DUF3384 54 470 4e-103 PFAM
Pfam:Tuberin 555 903 5.9e-149 PFAM
low complexity region 1023 1054 N/A INTRINSIC
low complexity region 1271 1278 N/A INTRINSIC
low complexity region 1310 1328 N/A INTRINSIC
low complexity region 1330 1344 N/A INTRINSIC
low complexity region 1378 1398 N/A INTRINSIC
Pfam:Rap_GAP 1497 1685 1.3e-43 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226242
Predicted Effect probably benign
Transcript: ENSMUST00000226284
AA Change: Y686C

PolyPhen 2 Score 0.054 (Sensitivity: 0.94; Specificity: 0.84)
Predicted Effect possibly damaging
Transcript: ENSMUST00000226398
AA Change: Y686C

PolyPhen 2 Score 0.907 (Sensitivity: 0.81; Specificity: 0.94)
Predicted Effect possibly damaging
Transcript: ENSMUST00000227607
AA Change: Y627C

PolyPhen 2 Score 0.807 (Sensitivity: 0.84; Specificity: 0.93)
Predicted Effect probably damaging
Transcript: ENSMUST00000227745
AA Change: Y686C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
Predicted Effect probably damaging
Transcript: ENSMUST00000228412
AA Change: Y686C

PolyPhen 2 Score 0.985 (Sensitivity: 0.74; Specificity: 0.96)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000228220
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227754
Meta Mutation Damage Score 0.4547 question?
Coding Region Coverage
  • 1x: 98.8%
  • 3x: 97.7%
  • 10x: 94.0%
  • 20x: 84.7%
Validation Efficiency 95% (94/99)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Mutations in this gene lead to tuberous sclerosis complex. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. The protein associates with hamartin in a cytosolic complex, possibly acting as a chaperone for hamartin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mutants exhibit liver hypoplasia, open neural tube, thickened myocardium and die by embryonic day 9.5-12.5. Heterozygotes develop renal cystadenomas, liver hemangiomas (sometimes resulting in fatal bleeding) and lung adenomas. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 91 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930447C04Rik T G 12: 72,928,195 (GRCm39) N512T possibly damaging Het
Aadacl2 A T 3: 59,932,313 (GRCm39) H276L probably damaging Het
Adam12 G A 7: 133,533,543 (GRCm39) T445M probably benign Het
Ash2l A T 8: 26,317,406 (GRCm39) F290L probably benign Het
Asxl3 C T 18: 22,658,281 (GRCm39) P2097L probably benign Het
Atmin A G 8: 117,684,115 (GRCm39) I592V probably damaging Het
Atxn2 T C 5: 121,941,145 (GRCm39) probably null Het
BC004004 T C 17: 29,515,665 (GRCm39) probably null Het
Cacna1e T C 1: 154,437,552 (GRCm39) N328S possibly damaging Het
Cacna2d1 A T 5: 16,560,493 (GRCm39) K765I probably damaging Het
Cc2d1a A G 8: 84,860,604 (GRCm39) probably null Het
Ccdc28b A G 4: 129,514,408 (GRCm39) V198A probably benign Het
Ces1b G T 8: 93,794,736 (GRCm39) R288S probably damaging Het
Cfap100 T G 6: 90,389,166 (GRCm39) T198P probably benign Het
Clint1 T C 11: 45,781,610 (GRCm39) S227P probably damaging Het
Cntn5 C A 9: 10,145,344 (GRCm39) C122F probably damaging Het
Col3a1 A G 1: 45,382,472 (GRCm39) probably null Het
Cyp4a10 A C 4: 115,386,646 (GRCm39) D431A probably damaging Het
Cyp4f16 CTATG CTATGTATG 17: 32,769,708 (GRCm39) probably null Het
Dlc1 A T 8: 37,060,617 (GRCm39) probably benign Het
Dlgap2 T C 8: 14,777,060 (GRCm39) S102P probably benign Het
Dnah7b G A 1: 46,117,753 (GRCm39) probably benign Het
Dock10 A C 1: 80,526,853 (GRCm39) S1124A probably benign Het
Dscam C T 16: 96,621,151 (GRCm39) R519H probably damaging Het
Efcab3 A T 11: 104,999,581 (GRCm39) probably benign Het
Evi2a G T 11: 79,418,096 (GRCm39) N171K probably damaging Het
Fbxl15 T C 19: 46,318,684 (GRCm39) L286P probably damaging Het
Fpr1 T A 17: 18,097,525 (GRCm39) I155F probably benign Het
Gcat C T 15: 78,918,194 (GRCm39) A84V probably null Het
Gls A G 1: 52,230,293 (GRCm39) F473L possibly damaging Het
Gnat1 T C 9: 107,554,164 (GRCm39) D169G probably damaging Het
Grm3 A C 5: 9,639,958 (GRCm39) M29R probably benign Het
Herc1 A T 9: 66,375,085 (GRCm39) D3303V probably damaging Het
Ibsp G A 5: 104,458,405 (GRCm39) G314D unknown Het
Irag2 C T 6: 145,120,237 (GRCm39) T484M possibly damaging Het
Lgr6 C A 1: 134,915,210 (GRCm39) A513S probably damaging Het
Lrriq4 T A 3: 30,704,910 (GRCm39) C313S probably damaging Het
Marchf10 G T 11: 105,281,409 (GRCm39) T292K probably damaging Het
Mcoln2 C A 3: 145,896,137 (GRCm39) Y6* probably null Het
Mup4 A G 4: 59,958,076 (GRCm39) I164T probably damaging Het
Myo1b T C 1: 51,817,717 (GRCm39) probably benign Het
Ncam1 A G 9: 49,456,100 (GRCm39) I506T probably damaging Het
Notch1 A T 2: 26,370,976 (GRCm39) probably benign Het
Nr4a3 A T 4: 48,051,777 (GRCm39) Q177L probably benign Het
Nsun4 A G 4: 115,910,147 (GRCm39) S138P possibly damaging Het
Or1a1 A G 11: 74,086,505 (GRCm39) M59V probably damaging Het
Or2b6 G T 13: 21,823,560 (GRCm39) N44K probably benign Het
Or2d36 A T 7: 106,747,405 (GRCm39) N294I probably damaging Het
Or4k5 T C 14: 50,385,815 (GRCm39) N172S probably damaging Het
Pagr1a A T 7: 126,615,469 (GRCm39) probably benign Het
Pcdhb2 A T 18: 37,429,343 (GRCm39) I82L probably benign Het
Pds5b A T 5: 150,677,882 (GRCm39) N500I probably damaging Het
Pik3r6 A T 11: 68,422,271 (GRCm39) E223D possibly damaging Het
Pkhd1l1 A T 15: 44,404,384 (GRCm39) probably benign Het
Prex1 T C 2: 166,422,383 (GRCm39) D1204G probably damaging Het
Prickle1 C T 15: 93,402,955 (GRCm39) E244K possibly damaging Het
Ptprd A T 4: 76,002,789 (GRCm39) V211E probably damaging Het
Rad51d G A 11: 82,781,179 (GRCm39) R23* probably null Het
Rapgef6 G A 11: 54,517,534 (GRCm39) G262R probably damaging Het
Reln A G 5: 22,333,600 (GRCm39) probably benign Het
Rev1 T C 1: 38,127,286 (GRCm39) T325A probably damaging Het
Rnd3 T A 2: 51,022,518 (GRCm39) I175L probably benign Het
Rp1 C A 1: 4,417,619 (GRCm39) L1164F probably damaging Het
S100a7a T C 3: 90,562,942 (GRCm39) V43A probably benign Het
Scaper A C 9: 55,510,202 (GRCm39) Y1104* probably null Het
Scn2a T A 2: 65,594,938 (GRCm39) V1929D probably benign Het
Scn3a T C 2: 65,359,785 (GRCm39) N141S possibly damaging Het
Slc12a7 T G 13: 73,949,127 (GRCm39) L718R probably damaging Het
Slc15a2 T C 16: 36,605,005 (GRCm39) probably benign Het
Slc35b3 G A 13: 39,138,110 (GRCm39) Q100* probably null Het
Slc9a5 T A 8: 106,081,785 (GRCm39) V170E possibly damaging Het
Snx5 T G 2: 144,096,731 (GRCm39) K278T possibly damaging Het
Sorbs2 T C 8: 46,243,000 (GRCm39) probably benign Het
Stab1 C T 14: 30,873,647 (GRCm39) W1008* probably null Het
Stab2 C T 10: 86,697,231 (GRCm39) probably null Het
Tacc3 A G 5: 33,825,321 (GRCm39) E377G probably benign Het
Tango6 T C 8: 107,415,671 (GRCm39) L164P probably damaging Het
Tbc1d12 T A 19: 38,902,796 (GRCm39) S570T possibly damaging Het
Thbs1 T C 2: 117,944,836 (GRCm39) F217L probably damaging Het
Tmbim6 T A 15: 99,300,004 (GRCm39) V40E probably damaging Het
Tmigd1 A T 11: 76,800,986 (GRCm39) N158Y probably damaging Het
Top3b C T 16: 16,710,641 (GRCm39) R824* probably null Het
Tram1l1 A T 3: 124,115,580 (GRCm39) K247* probably null Het
Tsga10 T C 1: 37,858,680 (GRCm39) Q218R probably damaging Het
Uba6 G T 5: 86,288,282 (GRCm39) A439D probably damaging Het
Ubn1 C A 16: 4,895,158 (GRCm39) P735T probably damaging Het
Usp40 A G 1: 87,909,808 (GRCm39) S549P probably benign Het
Utp20 T C 10: 88,655,201 (GRCm39) T176A probably benign Het
Utp4 T G 8: 107,624,685 (GRCm39) probably benign Het
Xpo5 C T 17: 46,518,853 (GRCm39) probably benign Het
Zfp979 A T 4: 147,698,493 (GRCm39) I72K possibly damaging Het
Other mutations in Tsc2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00231:Tsc2 APN 17 24,827,081 (GRCm39) missense probably damaging 1.00
IGL00985:Tsc2 APN 17 24,816,105 (GRCm39) missense probably damaging 1.00
IGL01386:Tsc2 APN 17 24,832,259 (GRCm39) missense probably damaging 1.00
IGL01468:Tsc2 APN 17 24,840,071 (GRCm39) missense possibly damaging 0.90
IGL01530:Tsc2 APN 17 24,841,636 (GRCm39) missense possibly damaging 0.76
IGL02390:Tsc2 APN 17 24,819,427 (GRCm39) missense probably damaging 1.00
IGL02398:Tsc2 APN 17 24,840,703 (GRCm39) missense probably damaging 1.00
IGL02741:Tsc2 APN 17 24,848,943 (GRCm39) missense probably damaging 1.00
IGL03191:Tsc2 APN 17 24,847,028 (GRCm39) missense probably damaging 1.00
IGL03372:Tsc2 APN 17 24,838,444 (GRCm39) missense probably damaging 1.00
IGL03412:Tsc2 APN 17 24,816,042 (GRCm39) missense probably damaging 0.98
Twitch UTSW 17 24,815,716 (GRCm39) splice site probably null
PIT4515001:Tsc2 UTSW 17 24,840,121 (GRCm39) missense probably benign 0.15
R0025:Tsc2 UTSW 17 24,849,978 (GRCm39) splice site probably benign
R0025:Tsc2 UTSW 17 24,849,978 (GRCm39) splice site probably benign
R0138:Tsc2 UTSW 17 24,818,600 (GRCm39) missense possibly damaging 0.65
R0540:Tsc2 UTSW 17 24,840,686 (GRCm39) missense probably damaging 1.00
R0570:Tsc2 UTSW 17 24,845,701 (GRCm39) missense probably damaging 1.00
R0607:Tsc2 UTSW 17 24,840,686 (GRCm39) missense probably damaging 1.00
R0826:Tsc2 UTSW 17 24,815,932 (GRCm39) missense probably benign 0.04
R1430:Tsc2 UTSW 17 24,817,997 (GRCm39) critical splice donor site probably null
R1466:Tsc2 UTSW 17 24,827,947 (GRCm39) missense probably damaging 1.00
R1466:Tsc2 UTSW 17 24,827,947 (GRCm39) missense probably damaging 1.00
R1541:Tsc2 UTSW 17 24,850,950 (GRCm39) missense probably damaging 1.00
R1717:Tsc2 UTSW 17 24,816,042 (GRCm39) missense probably damaging 0.98
R1799:Tsc2 UTSW 17 24,823,382 (GRCm39) missense probably benign
R2030:Tsc2 UTSW 17 24,842,444 (GRCm39) splice site probably benign
R2147:Tsc2 UTSW 17 24,840,116 (GRCm39) missense possibly damaging 0.62
R2888:Tsc2 UTSW 17 24,850,969 (GRCm39) critical splice donor site probably null
R3609:Tsc2 UTSW 17 24,841,524 (GRCm39) missense possibly damaging 0.74
R3610:Tsc2 UTSW 17 24,841,524 (GRCm39) missense possibly damaging 0.74
R3811:Tsc2 UTSW 17 24,848,011 (GRCm39) missense probably benign 0.09
R3895:Tsc2 UTSW 17 24,818,786 (GRCm39) missense probably damaging 1.00
R3962:Tsc2 UTSW 17 24,840,140 (GRCm39) splice site probably benign
R3971:Tsc2 UTSW 17 24,842,562 (GRCm39) missense probably damaging 1.00
R4018:Tsc2 UTSW 17 24,844,255 (GRCm39) missense probably damaging 0.99
R4184:Tsc2 UTSW 17 24,850,990 (GRCm39) missense probably benign 0.43
R4435:Tsc2 UTSW 17 24,818,687 (GRCm39) missense probably benign 0.01
R4437:Tsc2 UTSW 17 24,818,687 (GRCm39) missense probably benign 0.01
R4474:Tsc2 UTSW 17 24,816,238 (GRCm39) missense probably damaging 0.98
R4703:Tsc2 UTSW 17 24,823,883 (GRCm39) missense probably benign 0.13
R4731:Tsc2 UTSW 17 24,822,249 (GRCm39) missense possibly damaging 0.72
R4732:Tsc2 UTSW 17 24,822,249 (GRCm39) missense possibly damaging 0.72
R4733:Tsc2 UTSW 17 24,822,249 (GRCm39) missense possibly damaging 0.72
R4817:Tsc2 UTSW 17 24,815,716 (GRCm39) splice site probably null
R4890:Tsc2 UTSW 17 24,819,009 (GRCm39) missense probably damaging 1.00
R4922:Tsc2 UTSW 17 24,819,343 (GRCm39) missense probably benign 0.22
R5119:Tsc2 UTSW 17 24,822,254 (GRCm39) missense probably benign 0.00
R5393:Tsc2 UTSW 17 24,819,370 (GRCm39) missense possibly damaging 0.89
R5785:Tsc2 UTSW 17 24,818,861 (GRCm39) splice site probably null
R5838:Tsc2 UTSW 17 24,832,190 (GRCm39) missense probably benign 0.01
R5857:Tsc2 UTSW 17 24,818,981 (GRCm39) missense probably damaging 0.99
R5911:Tsc2 UTSW 17 24,819,361 (GRCm39) missense possibly damaging 0.63
R5988:Tsc2 UTSW 17 24,839,740 (GRCm39) missense probably damaging 1.00
R6275:Tsc2 UTSW 17 24,819,394 (GRCm39) missense probably benign 0.00
R6290:Tsc2 UTSW 17 24,815,884 (GRCm39) missense probably benign 0.04
R6371:Tsc2 UTSW 17 24,845,688 (GRCm39) missense probably benign 0.00
R6467:Tsc2 UTSW 17 24,828,101 (GRCm39) missense probably benign 0.04
R6577:Tsc2 UTSW 17 24,829,473 (GRCm39) missense probably damaging 1.00
R6728:Tsc2 UTSW 17 24,840,098 (GRCm39) missense probably damaging 1.00
R6918:Tsc2 UTSW 17 24,832,203 (GRCm39) missense probably damaging 1.00
R6995:Tsc2 UTSW 17 24,847,028 (GRCm39) missense probably damaging 1.00
R7026:Tsc2 UTSW 17 24,845,713 (GRCm39) missense probably damaging 0.99
R7136:Tsc2 UTSW 17 24,832,254 (GRCm39) missense probably benign 0.00
R7236:Tsc2 UTSW 17 24,842,568 (GRCm39) missense possibly damaging 0.82
R7243:Tsc2 UTSW 17 24,818,604 (GRCm39) missense probably benign 0.02
R7249:Tsc2 UTSW 17 24,826,729 (GRCm39) missense probably damaging 1.00
R7450:Tsc2 UTSW 17 24,819,005 (GRCm39) missense probably damaging 1.00
R7522:Tsc2 UTSW 17 24,849,939 (GRCm39) missense probably damaging 1.00
R7529:Tsc2 UTSW 17 24,816,922 (GRCm39) missense probably damaging 0.98
R7637:Tsc2 UTSW 17 24,826,466 (GRCm39) missense probably benign 0.13
R7781:Tsc2 UTSW 17 24,827,089 (GRCm39) missense possibly damaging 0.52
R8005:Tsc2 UTSW 17 24,818,570 (GRCm39) missense probably damaging 0.98
R8262:Tsc2 UTSW 17 24,833,340 (GRCm39) missense probably benign 0.06
R8268:Tsc2 UTSW 17 24,818,984 (GRCm39) missense probably benign 0.44
R8400:Tsc2 UTSW 17 24,823,961 (GRCm39) missense possibly damaging 0.62
R9020:Tsc2 UTSW 17 24,845,691 (GRCm39) missense probably damaging 0.99
R9039:Tsc2 UTSW 17 24,826,489 (GRCm39) missense probably benign 0.01
R9065:Tsc2 UTSW 17 24,822,164 (GRCm39) missense probably benign 0.39
R9123:Tsc2 UTSW 17 24,823,802 (GRCm39) missense probably null 0.40
R9125:Tsc2 UTSW 17 24,823,802 (GRCm39) missense probably null 0.40
R9186:Tsc2 UTSW 17 24,823,862 (GRCm39) missense probably damaging 1.00
R9390:Tsc2 UTSW 17 24,823,824 (GRCm39) missense probably damaging 1.00
R9542:Tsc2 UTSW 17 24,819,308 (GRCm39) critical splice donor site probably null
R9721:Tsc2 UTSW 17 24,818,616 (GRCm39) nonsense probably null
Z1177:Tsc2 UTSW 17 24,839,753 (GRCm39) missense possibly damaging 0.61
Predicted Primers PCR Primer
(F):5'- TCAGACTCACCTGGTAGATGCTCC -3'
(R):5'- GTGAGATTCAGCCCTTACTGCCTC -3'

Sequencing Primer
(F):5'- CCTGGTAGATGCTCCTAAGACAG -3'
(R):5'- CCTACTCAGGGTTATTTCATAGGAG -3'
Posted On 2014-03-14