Mutagenetix > Incidental Mutation

Incidental Mutation 'R8005:Tsc2'

616600

Institutional Source

Beutler Lab

Gene Symbol

Tsc2

Ensembl Gene

ENSMUSG00000002496

Gene Name

tuberous sclerosis 2

Synonyms

tuberin, Nafld

MMRRC Submission

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R8005 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

24595816-24632630 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 24599596 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Valine at position 1423 (A1423V)

Ref Sequence

ENSEMBL: ENSMUSP00000094986 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000035565] [ENSMUST00000097373] [ENSMUST00000226284] [ENSMUST00000226398] [ENSMUST00000227607] [ENSMUST00000227745] [ENSMUST00000227804] [ENSMUST00000228412]

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: A1423V

PolyPhen 2 Score 0.983 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000094986
Gene: ENSMUSG00000002496
AA Change: A1423V

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

probably damaging
Transcript: ENSMUST00000226284
AA Change: A1466V

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)

Predicted Effect

probably damaging
Transcript: ENSMUST00000226398
AA Change: A1423V

PolyPhen 2 Score 0.983 (Sensitivity: 0.75; Specificity: 0.96)

Predicted Effect

probably benign
Transcript: ENSMUST00000227107

Predicted Effect

probably benign
Transcript: ENSMUST00000227607

Predicted Effect

probably benign
Transcript: ENSMUST00000227745
AA Change: A1489V

PolyPhen 2 Score 0.289 (Sensitivity: 0.91; Specificity: 0.88)

Predicted Effect

probably benign
Transcript: ENSMUST00000227804

Predicted Effect

probably benign
Transcript: ENSMUST00000228412
AA Change: A1422V

PolyPhen 2 Score 0.289 (Sensitivity: 0.91; Specificity: 0.88)

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

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: 60 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acot1	A	G	12: 84,017,000	D294G	probably benign	Het
Ak8	A	T	2: 28,712,302	S83C	probably benign	Het
Ankrd34b	C	A	13: 92,438,722	A154E	possibly damaging	Het
Anks1	A	G	17: 28,059,367	D1175G	probably damaging	Het
Ano4	T	A	10: 88,971,321	L799F	probably benign	Het
Aplp1	T	C	7: 30,436,045		probably null	Het
Apob	A	T	12: 8,009,744	H2742L	probably benign	Het
Apol7e	C	T	15: 77,718,077	Q292*	probably null	Het
Atp2b1	G	A	10: 98,994,799	G374D	probably damaging	Het
B020004J07Rik	A	G	4: 101,837,251	V145A	probably damaging	Het
B4galt5	A	G	2: 167,301,464	S347P	probably damaging	Het
Bcl11b	T	C	12: 107,916,197	T620A	probably benign	Het
Bco2	T	A	9: 50,538,913	D329V	probably damaging	Het
Cemip	C	A	7: 84,003,408		probably benign	Het
Copg2	T	A	6: 30,896,697	M1L	possibly damaging	Het
D430041D05Rik	G	A	2: 104,258,254	H164Y	possibly damaging	Het
Dscaml1	G	T	9: 45,717,510	G1121C	probably damaging	Het
Fam208b	C	T	13: 3,575,681	S1423N	probably benign	Het
Gas2l1	A	T	11: 5,061,552	S426T	probably benign	Het
Gm17783	T	C	16: 45,532,037		probably benign	Het
Gm9195	T	A	14: 72,426,400	I2740F	probably benign	Het
Irgm1	A	G	11: 48,866,390	I214T	probably damaging	Het
Kbtbd3	C	T	9: 4,330,655	T343I	probably damaging	Het
Ldlrad1	G	A	4: 107,209,491	A8T	probably benign	Het
Ly75	A	T	2: 60,332,934	Y804N	probably damaging	Het
Mgat2	A	G	12: 69,185,948	H432R	probably damaging	Het
Nsrp1	A	T	11: 77,045,786	M528K	probably damaging	Het
Nup54	T	C	5: 92,428,147	I162V	probably benign	Het
Obsl1	T	A	1: 75,505,452	N258I	probably damaging	Het
Olfr10	G	T	11: 49,318,141	M198I	probably benign	Het
Olfr350	A	G	2: 36,850,144	T33A	probably benign	Het
Olfr478	T	C	7: 108,032,263	R27G	possibly damaging	Het
Olfr498	T	C	7: 108,465,486	V54A	probably benign	Het
Pax2	G	A	19: 44,760,889	V20M	probably damaging	Het
Pigb	A	T	9: 73,015,264	M13K	unknown	Het
Pigt	CCAGGCCAGTGAGTAGGTTTGTCTCTGTCTAGTGTGGATCTGTAACCACAGGCCAGTGAGTAGGTTTGTCTCTGTCTAGTGTGGATCTGTAACCACAGGCCAGTGAGTAGGTTTGTCTCTGTCTAGTGTGGAT	CCAGGCCAGTGAGTAGGTTTGTCTCTGTCTAGTGTGGATCTGTAACCACAGGCCAGTGAGTAGGTTTGTCTCTGTCTAGTGTGGAT	2: 164,499,669		probably null	Het
Pik3c2a	T	C	7: 116,418,036	Y162C	probably damaging	Het
Pik3c2g	A	T	6: 139,622,069	D61V	probably benign	Het
Plscr4	C	T	9: 92,490,790	R322*	probably null	Het
Prss46	A	G	9: 110,856,076	D256G	probably benign	Het
Rims1	G	T	1: 22,412,213	D196E		Het
Sbf1	A	G	15: 89,294,205	L1498P	probably damaging	Het
Sh2b1	T	C	7: 126,469,307	D444G	possibly damaging	Het
Slc7a15	T	G	12: 8,539,395	M51L	probably damaging	Het
Slitrk1	T	C	14: 108,913,265	I5V	probably benign	Het
Spg20	T	A	3: 55,117,352	C123S	probably benign	Het
Sry	C	T	Y: 2,663,303	R119K	possibly damaging	Het
Tbcc	T	C	17: 46,890,760	V24A	possibly damaging	Het
Tfap2a	T	A	13: 40,719,208	M331L	possibly damaging	Het
Thnsl1	A	G	2: 21,211,944	I170V	probably benign	Het
Ticrr	T	G	7: 79,694,048	S1220R	probably damaging	Het
Tmem262	T	C	19: 6,080,477	M77T	possibly damaging	Het
Tmem67	A	G	4: 12,047,821	S771P	probably damaging	Het
Ubr4	T	A	4: 139,412,630	Y1175N	probably damaging	Het
Usp25	G	A	16: 77,077,068	A511T	probably benign	Het
Vmn2r115	T	A	17: 23,344,150	Y58*	probably null	Het
Wt1	T	C	2: 105,127,444		probably null	Het
Zfp735	A	T	11: 73,712,314	K695*	probably null	Het
Zkscan14	A	G	5: 145,195,758	F321S	possibly damaging	Het
Zswim9	T	C	7: 13,261,138	E364G	probably damaging	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
R4890:Tsc2	UTSW	17	24600035	missense	probably damaging	1.00
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
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'- TTATGGCTCCCACCAGCTAC -3'
(R):5'- ATTGATATTGGACGGCTGAGTC -3'

Sequencing Primer
(F):5'- TACAGGAAGACACAATTCATGACTG -3'
(R):5'- TGAGTCCTGAGGCTAAGGTCC -3'

Posted On

2020-01-23