Mutagenetix > Incidental Mutation

Incidental Mutation 'R4890:Tsc2'

377285

Institutional Source

Beutler Lab

Gene Symbol

Tsc2

Ensembl Gene

ENSMUSG00000002496

Gene Name

tuberous sclerosis 2

Synonyms

tuberin, Nafld

MMRRC Submission

042495-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4890 (G1)

Quality Score

214

Status

Validated

Chromosome

Chromosomal Location

24595816-24632630 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 24600035 bp (GRCm38)

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] [ENSMUST00000227607] [ENSMUST00000227745] [ENSMUST00000228412] [ENSMUST00000227804]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000035565

SMART Domains

Protein: ENSMUSP00000049296
Gene: ENSMUSG00000032855

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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

noncoding transcript
Transcript: ENSMUST00000226473

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000226691

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000226985

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227094

Predicted Effect

probably benign
Transcript: ENSMUST00000227107

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227330

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227432

Predicted Effect

probably damaging
Transcript: ENSMUST00000227607
AA Change: S1218T

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

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 benign
Transcript: ENSMUST00000227658

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000228729

Predicted Effect

probably benign
Transcript: ENSMUST00000227804

Meta Mutation Damage Score

0.0787

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
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700080E11Rik	A	T	9: 105,144,587	S87T	possibly damaging	Het
AA986860	T	C	1: 130,740,988		probably benign	Het
Adcy4	C	T	14: 55,779,029	D322N	probably damaging	Het
Adgrb3	T	C	1: 25,221,827	N916S	probably damaging	Het
AI464131	G	A	4: 41,498,877	T251M	probably benign	Het
Aox2	T	C	1: 58,334,703	V841A	probably benign	Het
Baz2b	A	T	2: 59,926,039	M983K	probably damaging	Het
BC027072	C	T	17: 71,752,311	V124I	possibly damaging	Het
C2cd2l	A	G	9: 44,311,133	F682L	probably damaging	Het
Ccsap	T	G	8: 123,845,421	E114A	possibly damaging	Het
Cept1	T	A	3: 106,505,807	T201S	probably damaging	Het
Cfap221	T	C	1: 119,955,746	M232V	probably benign	Het
Chsy1	A	G	7: 66,110,226	R106G	probably benign	Het
Cit	C	T	5: 115,988,123		probably benign	Het
Cldn7	G	A	11: 69,967,092	V42I	probably benign	Het
Cnnm4	T	A	1: 36,472,264	V191E	probably benign	Het
Cntf	A	T	19: 12,763,962	V178D	possibly damaging	Het
Ctsz	C	A	2: 174,428,600	R263L	probably damaging	Het
Dclk1	T	C	3: 55,521,932	M407T	probably benign	Het
Dennd1a	A	T	2: 38,176,226		probably benign	Het
Dnhd1	A	G	7: 105,656,957	I368V	possibly damaging	Het
Fam159a	A	G	4: 108,367,801	V188A	probably benign	Het
Gak	A	T	5: 108,580,876		probably benign	Het
Gm12794	A	G	4: 101,941,591	E253G	probably damaging	Het
Gm9268	A	G	7: 43,047,600	R687G	probably damaging	Het
Hepacam2	A	T	6: 3,487,231	V42D	probably damaging	Het
Il1rl2	CTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATT	CTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATT	1: 40,327,310		probably benign	Het
Insr	T	A	8: 3,198,234	Q437L	probably benign	Het
Itga8	G	A	2: 12,193,291		probably benign	Het
Kansl1	A	T	11: 104,343,042	C732S	probably benign	Het
Kdsr	T	C	1: 106,753,234	K78R	probably benign	Het
Kif14	T	C	1: 136,487,130	S785P	possibly damaging	Het
Lbr	C	A	1: 181,817,568	L506F	probably benign	Het
Macf1	C	A	4: 123,448,238	C2720F	probably damaging	Het
Mapt	G	A	11: 104,328,149	D738N	probably damaging	Het
Mroh9	T	C	1: 163,026,524	Y769C	probably damaging	Het
Mylk2	A	G	2: 152,920,354	N515S	possibly damaging	Het
Nek10	T	A	14: 14,860,986	L513M	possibly damaging	Het
Nrxn2	A	T	19: 6,448,278	S258C	possibly damaging	Het
Olfr1024	C	T	2: 85,904,748	C102Y	possibly damaging	Het
Olfr1346	T	A	7: 6,474,849	C246*	probably null	Het
Olfr672	G	A	7: 104,996,104	H267Y	probably benign	Het
Olfr786	C	T	10: 129,437,079	T89I	probably benign	Het
Olfr893	G	T	9: 38,209,290	C79F	probably benign	Het
Osgin2	G	A	4: 16,013,739		probably benign	Het
Otud3	G	A	4: 138,913,749	R27W	probably damaging	Het
Pcdhga12	T	A	18: 37,768,237	F707L	possibly damaging	Het
Pik3r1	T	C	13: 101,757,610	E17G	probably damaging	Het
Prickle4	AAGAGAGAGAGAGAGA	AAGAGAGAGAGAGA	17: 47,689,881		probably benign	Het
Prokr1	G	A	6: 87,588,696	R56W	probably benign	Het
Ptprz1	G	A	6: 23,024,958	C1731Y	probably damaging	Het
Rbm15b	A	T	9: 106,885,829	F380Y	possibly damaging	Het
Rfc5	G	A	5: 117,386,820	L56F	probably damaging	Het
Rhpn2	A	T	7: 35,390,803	M617L	probably benign	Het
Rusc1	T	C	3: 89,088,270		probably null	Het
Sec23ip	A	G	7: 128,752,910	N297D	probably damaging	Het
Sema3c	A	T	5: 17,675,159	H259L	probably benign	Het
Sgsm1	G	A	5: 113,280,462		probably benign	Het
Sipa1l2	T	A	8: 125,491,867	S244C	probably damaging	Het
Slc39a5	T	C	10: 128,398,447	I196V	probably benign	Het
Smim22	G	A	16: 5,007,858	A36T	probably damaging	Het
Spag6	A	G	2: 18,742,777	I408V	probably benign	Het
Sult2a5	A	G	7: 13,625,386	I96V	probably benign	Het
Tmcc2	C	A	1: 132,380,779	A126S	probably benign	Het
Ttc21a	A	G	9: 119,959,037	S843G	probably benign	Het
Tubd1	G	C	11: 86,552,795	V110L	possibly damaging	Het
Ugt1a2	T	A	1: 88,200,812	V59D	probably damaging	Het
Vsig8	T	A	1: 172,561,575	H131Q	probably benign	Het
Zbtb42	C	A	12: 112,680,427	Y345*	probably null	Het
Zfp612	T	A	8: 110,089,944	C594*	probably null	Het
Zfp940	A	G	7: 29,845,399	V361A	probably benign	Het

Other mutations in Tsc2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00231:Tsc2	APN	17	24608107	missense	probably damaging	1.00
IGL00985:Tsc2	APN	17	24597131	missense	probably damaging	1.00
IGL01386:Tsc2	APN	17	24613285	missense	probably damaging	1.00
IGL01468:Tsc2	APN	17	24621097	missense	possibly damaging	0.90
IGL01530:Tsc2	APN	17	24622662	missense	possibly damaging	0.76
IGL02390:Tsc2	APN	17	24600453	missense	probably damaging	1.00
IGL02398:Tsc2	APN	17	24621729	missense	probably damaging	1.00
IGL02741:Tsc2	APN	17	24629969	missense	probably damaging	1.00
IGL03191:Tsc2	APN	17	24628054	missense	probably damaging	1.00
IGL03372:Tsc2	APN	17	24619470	missense	probably damaging	1.00
IGL03412:Tsc2	APN	17	24597068	missense	probably damaging	0.98
Twitch	UTSW	17	24596742	splice site	probably null
PIT4515001:Tsc2	UTSW	17	24621147	missense	probably benign	0.15
R0025:Tsc2	UTSW	17	24631004	splice site	probably benign
R0025:Tsc2	UTSW	17	24631004	splice site	probably benign
R0138:Tsc2	UTSW	17	24599626	missense	possibly damaging	0.65
R0540:Tsc2	UTSW	17	24621712	missense	probably damaging	1.00
R0570:Tsc2	UTSW	17	24626727	missense	probably damaging	1.00
R0607:Tsc2	UTSW	17	24621712	missense	probably damaging	1.00
R0826:Tsc2	UTSW	17	24596958	missense	probably benign	0.04
R1430:Tsc2	UTSW	17	24599023	critical splice donor site	probably null
R1440:Tsc2	UTSW	17	24614392	missense	probably damaging	1.00
R1466:Tsc2	UTSW	17	24608973	missense	probably damaging	1.00
R1466:Tsc2	UTSW	17	24608973	missense	probably damaging	1.00
R1541:Tsc2	UTSW	17	24631976	missense	probably damaging	1.00
R1717:Tsc2	UTSW	17	24597068	missense	probably damaging	0.98
R1799:Tsc2	UTSW	17	24604408	missense	probably benign
R2030:Tsc2	UTSW	17	24623470	splice site	probably benign
R2147:Tsc2	UTSW	17	24621142	missense	possibly damaging	0.62
R2888:Tsc2	UTSW	17	24631995	critical splice donor site	probably null
R3609:Tsc2	UTSW	17	24622550	missense	possibly damaging	0.74
R3610:Tsc2	UTSW	17	24622550	missense	possibly damaging	0.74
R3811:Tsc2	UTSW	17	24629037	missense	probably benign	0.09
R3895:Tsc2	UTSW	17	24599812	missense	probably damaging	1.00
R3962:Tsc2	UTSW	17	24621166	splice site	probably benign
R3971:Tsc2	UTSW	17	24623588	missense	probably damaging	1.00
R4018:Tsc2	UTSW	17	24625281	missense	probably damaging	0.99
R4184:Tsc2	UTSW	17	24632016	missense	probably benign	0.43
R4435:Tsc2	UTSW	17	24599713	missense	probably benign	0.01
R4437:Tsc2	UTSW	17	24599713	missense	probably benign	0.01
R4474:Tsc2	UTSW	17	24597264	missense	probably damaging	0.98
R4703:Tsc2	UTSW	17	24604909	missense	probably benign	0.13
R4731:Tsc2	UTSW	17	24603275	missense	possibly damaging	0.72
R4732:Tsc2	UTSW	17	24603275	missense	possibly damaging	0.72
R4733:Tsc2	UTSW	17	24603275	missense	possibly damaging	0.72
R4817:Tsc2	UTSW	17	24596742	splice site	probably null
R4922:Tsc2	UTSW	17	24600369	missense	probably benign	0.22
R5119:Tsc2	UTSW	17	24603280	missense	probably benign	0.00
R5393:Tsc2	UTSW	17	24600396	missense	possibly damaging	0.89
R5785:Tsc2	UTSW	17	24599887	splice site	probably null
R5838:Tsc2	UTSW	17	24613216	missense	probably benign	0.01
R5857:Tsc2	UTSW	17	24600007	missense	probably damaging	0.99
R5911:Tsc2	UTSW	17	24600387	missense	possibly damaging	0.63
R5988:Tsc2	UTSW	17	24620766	missense	probably damaging	1.00
R6275:Tsc2	UTSW	17	24600420	missense	probably benign	0.00
R6290:Tsc2	UTSW	17	24596910	missense	probably benign	0.04
R6371:Tsc2	UTSW	17	24626714	missense	probably benign	0.00
R6467:Tsc2	UTSW	17	24609127	missense	probably benign	0.04
R6577:Tsc2	UTSW	17	24610499	missense	probably damaging	1.00
R6728:Tsc2	UTSW	17	24621124	missense	probably damaging	1.00
R6918:Tsc2	UTSW	17	24613229	missense	probably damaging	1.00
R6995:Tsc2	UTSW	17	24628054	missense	probably damaging	1.00
R7026:Tsc2	UTSW	17	24626739	missense	probably damaging	0.99
R7136:Tsc2	UTSW	17	24613280	missense	probably benign	0.00
R7236:Tsc2	UTSW	17	24623594	missense	possibly damaging	0.82
R7243:Tsc2	UTSW	17	24599630	missense	probably benign	0.02
R7249:Tsc2	UTSW	17	24607755	missense	probably damaging	1.00
R7450:Tsc2	UTSW	17	24600031	missense	probably damaging	1.00
R7522:Tsc2	UTSW	17	24630965	missense	probably damaging	1.00
R7529:Tsc2	UTSW	17	24597948	missense	probably damaging	0.98
R7637:Tsc2	UTSW	17	24607492	missense	probably benign	0.13
R7781:Tsc2	UTSW	17	24608115	missense	possibly damaging	0.52
R8005:Tsc2	UTSW	17	24599596	missense	probably damaging	0.98
R8262:Tsc2	UTSW	17	24614366	missense	probably benign	0.06
R8268:Tsc2	UTSW	17	24600010	missense	probably benign	0.44
R8400:Tsc2	UTSW	17	24604987	missense	possibly damaging	0.62
R9020:Tsc2	UTSW	17	24626717	missense	probably damaging	0.99
R9039:Tsc2	UTSW	17	24607515	missense	probably benign	0.01
R9065:Tsc2	UTSW	17	24603190	missense	probably benign	0.39
R9123:Tsc2	UTSW	17	24604828	missense	probably null	0.40
R9125:Tsc2	UTSW	17	24604828	missense	probably null	0.40
R9186:Tsc2	UTSW	17	24604888	missense	probably damaging	1.00
R9390:Tsc2	UTSW	17	24604850	missense	probably damaging	1.00
R9542:Tsc2	UTSW	17	24600334	critical splice donor site	probably null
R9721:Tsc2	UTSW	17	24599642	nonsense	probably null
Z1177:Tsc2	UTSW	17	24620779	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