Incidental Mutation 'R4890:Tsc2'
ID 377285
Institutional Source Beutler Lab
Gene Symbol Tsc2
Ensembl Gene ENSMUSG00000002496
Gene Name TSC complex subunit 2
Synonyms tuberin, Nafld, tuberous sclerosis 2
MMRRC Submission 042495-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4890 (G1)
Quality Score 214
Status Validated
Chromosome 17
Chromosomal Location 24814790-24851604 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 24819009 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Threonine at position 1276 (S1276T)
Ref Sequence ENSEMBL: ENSMUSP00000154706 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000035565] [ENSMUST00000097373] [ENSMUST00000226284] [ENSMUST00000226398] [ENSMUST00000227745] [ENSMUST00000228412] [ENSMUST00000227607] [ENSMUST00000227804]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000035565
SMART Domains Protein: ENSMUSP00000049296
Gene: ENSMUSG00000032855

DomainStartEndE-ValueType
signal peptide 1 23 N/A INTRINSIC
LRRNT 32 71 1.61e-8 SMART
LRR_TYP 90 113 2.47e-5 SMART
LRRCT 125 177 3.84e-12 SMART
WSC 177 271 6.93e-34 SMART
PKD 272 355 2.72e-15 SMART
CLECT 406 530 5.72e-20 SMART
low complexity region 545 558 N/A INTRINSIC
low complexity region 763 788 N/A INTRINSIC
PKD 930 1008 1.06e-8 SMART
PKD 1015 1119 2.26e-12 SMART
PKD 1122 1205 2.03e-14 SMART
PKD 1208 1288 1.14e-17 SMART
PKD 1290 1373 2.35e-10 SMART
PKD 1374 1459 7.63e-10 SMART
PKD 1464 1541 1.95e-16 SMART
PKD 1544 1625 1.05e-16 SMART
PKD 1631 1714 1.93e-1 SMART
PKD 1716 1798 2.21e-15 SMART
PKD 1799 1882 5.7e-9 SMART
PKD 1884 1964 1.56e-6 SMART
PKD 1968 2056 3.1e-10 SMART
PKD 2057 2140 1.74e-13 SMART
Pfam:REJ 2167 2610 1e-108 PFAM
low complexity region 2697 2706 N/A INTRINSIC
GPS 3003 3052 1.33e-12 SMART
transmembrane domain 3065 3087 N/A INTRINSIC
LH2 3110 3224 3.5e-18 SMART
transmembrane domain 3275 3294 N/A INTRINSIC
transmembrane domain 3314 3336 N/A INTRINSIC
low complexity region 3357 3378 N/A INTRINSIC
low complexity region 3479 3492 N/A INTRINSIC
transmembrane domain 3547 3569 N/A INTRINSIC
low complexity region 3573 3591 N/A INTRINSIC
low complexity region 3626 3639 N/A INTRINSIC
low complexity region 3661 3676 N/A INTRINSIC
Pfam:PKD_channel 3701 4103 7.1e-125 PFAM
low complexity region 4153 4172 N/A INTRINSIC
low complexity region 4238 4256 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000097373
AA Change: S1277T

PolyPhen 2 Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000094986
Gene: ENSMUSG00000002496
AA Change: S1277T

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: ENSMUST00000116692
Predicted Effect probably damaging
Transcript: ENSMUST00000226284
AA Change: S1320T

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
Predicted Effect probably damaging
Transcript: ENSMUST00000226398
AA Change: S1277T

PolyPhen 2 Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226428
Predicted Effect probably damaging
Transcript: ENSMUST00000227745
AA Change: S1343T

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)
Predicted Effect probably damaging
Transcript: ENSMUST00000228412
AA Change: S1276T

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
Predicted Effect probably damaging
Transcript: ENSMUST00000227607
AA Change: S1218T

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
Predicted Effect probably benign
Transcript: ENSMUST00000227658
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227432
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226985
Predicted Effect probably benign
Transcript: ENSMUST00000227804
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227094
Predicted Effect probably benign
Transcript: ENSMUST00000227107
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227330
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226473
Predicted Effect noncoding transcript
Transcript: ENSMUST00000226691
Predicted Effect noncoding transcript
Transcript: ENSMUST00000228729
Meta Mutation Damage Score 0.0787 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.7%
  • 20x: 93.4%
Validation Efficiency 99% (81/82)
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: 71 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
AA986860 T C 1: 130,668,725 (GRCm39) probably benign Het
Adcy4 C T 14: 56,016,486 (GRCm39) D322N probably damaging Het
Adgrb3 T C 1: 25,260,908 (GRCm39) N916S probably damaging Het
Aox1 T C 1: 58,373,862 (GRCm39) V841A probably benign Het
Baz2b A T 2: 59,756,383 (GRCm39) M983K probably damaging Het
C2cd2l A G 9: 44,222,430 (GRCm39) F682L probably damaging Het
Ccsap T G 8: 124,572,160 (GRCm39) E114A possibly damaging Het
Cept1 T A 3: 106,413,123 (GRCm39) T201S probably damaging Het
Cfap221 T C 1: 119,883,476 (GRCm39) M232V probably benign Het
Chsy1 A G 7: 65,759,974 (GRCm39) R106G probably benign Het
Cit C T 5: 116,126,182 (GRCm39) probably benign Het
Cldn7 G A 11: 69,857,918 (GRCm39) V42I probably benign Het
Cnnm4 T A 1: 36,511,345 (GRCm39) V191E probably benign Het
Cntf A T 19: 12,741,326 (GRCm39) V178D possibly damaging Het
Ctsz C A 2: 174,270,393 (GRCm39) R263L probably damaging Het
Dclk1 T C 3: 55,429,353 (GRCm39) M407T probably benign Het
Dennd1a A T 2: 38,066,238 (GRCm39) probably benign Het
Dnhd1 A G 7: 105,306,164 (GRCm39) I368V possibly damaging Het
Gak A T 5: 108,728,742 (GRCm39) probably benign Het
Hepacam2 A T 6: 3,487,231 (GRCm39) V42D probably damaging Het
Il1rl2 CTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATT CTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATT 1: 40,366,470 (GRCm39) probably benign Het
Insr T A 8: 3,248,234 (GRCm39) Q437L probably benign Het
Itga8 G A 2: 12,198,102 (GRCm39) probably benign Het
Kansl1 A T 11: 104,233,868 (GRCm39) C732S probably benign Het
Kdsr T C 1: 106,680,964 (GRCm39) K78R probably benign Het
Kif14 T C 1: 136,414,868 (GRCm39) S785P possibly damaging Het
Lbr C A 1: 181,645,133 (GRCm39) L506F probably benign Het
Macf1 C A 4: 123,342,031 (GRCm39) C2720F probably damaging Het
Mapt G A 11: 104,218,975 (GRCm39) D738N probably damaging Het
Mroh9 T C 1: 162,854,093 (GRCm39) Y769C probably damaging Het
Mylk2 A G 2: 152,762,274 (GRCm39) N515S possibly damaging Het
Myorg G A 4: 41,498,877 (GRCm39) T251M probably benign Het
Nek10 T A 14: 14,860,986 (GRCm38) L513M possibly damaging Het
Nrxn2 A T 19: 6,498,308 (GRCm39) S258C possibly damaging Het
Nudt16l2 A T 9: 105,021,786 (GRCm39) S87T possibly damaging Het
Or52e15 G A 7: 104,645,311 (GRCm39) H267Y probably benign Het
Or5m12 C T 2: 85,735,092 (GRCm39) C102Y possibly damaging Het
Or6c1b C T 10: 129,272,948 (GRCm39) T89I probably benign Het
Or6z5 T A 7: 6,477,848 (GRCm39) C246* probably null Het
Or8c15 G T 9: 38,120,586 (GRCm39) C79F probably benign Het
Osgin2 G A 4: 16,013,739 (GRCm39) probably benign Het
Otud3 G A 4: 138,641,060 (GRCm39) R27W probably damaging Het
Pcare C T 17: 72,059,306 (GRCm39) V124I possibly damaging Het
Pcdhga12 T A 18: 37,901,290 (GRCm39) F707L possibly damaging Het
Pik3r1 T C 13: 101,894,118 (GRCm39) E17G probably damaging Het
Pramel19 A G 4: 101,798,788 (GRCm39) E253G probably damaging Het
Prickle4 AAGAGAGAGAGAGAGA AAGAGAGAGAGAGA 17: 48,000,806 (GRCm39) probably benign Het
Prokr1 G A 6: 87,565,678 (GRCm39) R56W probably benign Het
Ptprz1 G A 6: 23,024,957 (GRCm39) C1731Y probably damaging Het
Rbm15b A T 9: 106,763,028 (GRCm39) F380Y possibly damaging Het
Rfc5 G A 5: 117,524,885 (GRCm39) L56F probably damaging Het
Rhpn2 A T 7: 35,090,228 (GRCm39) M617L probably benign Het
Rusc1 T C 3: 88,995,577 (GRCm39) probably null Het
Sec23ip A G 7: 128,354,634 (GRCm39) N297D probably damaging Het
Sema3c A T 5: 17,880,157 (GRCm39) H259L probably benign Het
Sgsm1 G A 5: 113,428,328 (GRCm39) probably benign Het
Shisal2a A G 4: 108,224,998 (GRCm39) V188A probably benign Het
Sipa1l2 T A 8: 126,218,606 (GRCm39) S244C probably damaging Het
Slc39a5 T C 10: 128,234,316 (GRCm39) I196V probably benign Het
Smim22 G A 16: 4,825,722 (GRCm39) A36T probably damaging Het
Spag6 A G 2: 18,747,588 (GRCm39) I408V probably benign Het
Sult2a5 A G 7: 13,359,311 (GRCm39) I96V probably benign Het
Tmcc2 C A 1: 132,308,517 (GRCm39) A126S probably benign Het
Ttc21a A G 9: 119,788,103 (GRCm39) S843G probably benign Het
Tubd1 G C 11: 86,443,621 (GRCm39) V110L possibly damaging Het
Ugt1a2 T A 1: 88,128,534 (GRCm39) V59D probably damaging Het
Vmn2r-ps158 A G 7: 42,697,024 (GRCm39) R687G probably damaging Het
Vsig8 T A 1: 172,389,142 (GRCm39) H131Q probably benign Het
Zbtb42 C A 12: 112,646,861 (GRCm39) Y345* probably null Het
Zfp612 T A 8: 110,816,576 (GRCm39) C594* probably null Het
Zfp940 A G 7: 29,544,824 (GRCm39) V361A probably benign 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
R1440:Tsc2 UTSW 17 24,833,366 (GRCm39) missense probably damaging 1.00
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
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'- TGTCCTGTAAGGTCTGCAACTC -3'
(R):5'- CTGGCTCTGTACTGACTTGC -3'

Sequencing Primer
(F):5'- TGTAAGGTCTGCAACTCCGGAG -3'
(R):5'- TGAGCTGGATAGGCCTTCC -3'
Posted On 2016-03-17