Mutagenetix > Incidental Mutation

Incidental Mutation 'R5785:Tsc2'

447983

Institutional Source

Beutler Lab

Gene Symbol

Tsc2

Ensembl Gene

ENSMUSG00000002496

Gene Name

TSC complex subunit 2

Synonyms

tuberin, Nafld, tuberous sclerosis 2

MMRRC Submission

043206-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5785 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

24814790-24851604 bp(-) (GRCm39)

Type of Mutation

splice site

DNA Base Change (assembly)

T to C at 24818861 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000153864 (fasta)

Gene Model

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

possibly damaging
Transcript: ENSMUST00000097373
AA Change: E1326G

PolyPhen 2 Score 0.955 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000094986
Gene: ENSMUSG00000002496
AA Change: E1326G

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

possibly damaging
Transcript: ENSMUST00000226284
AA Change: E1369G

PolyPhen 2 Score 0.948 (Sensitivity: 0.79; Specificity: 0.95)

Predicted Effect

possibly damaging
Transcript: ENSMUST00000226398
AA Change: E1326G

PolyPhen 2 Score 0.955 (Sensitivity: 0.79; Specificity: 0.95)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000226428

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000226473

Predicted Effect

probably damaging
Transcript: ENSMUST00000228412
AA Change: E1325G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

Predicted Effect

probably damaging
Transcript: ENSMUST00000227607
AA Change: E1267G

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

Predicted Effect

probably benign
Transcript: ENSMUST00000227745
AA Change: E1392G

PolyPhen 2 Score 0.089 (Sensitivity: 0.93; Specificity: 0.85)

Predicted Effect

probably null
Transcript: ENSMUST00000227804

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000226691

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000228729

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227094

Predicted Effect

probably benign
Transcript: ENSMUST00000227107

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000226985

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227330

Predicted Effect

probably benign
Transcript: ENSMUST00000227658

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227432

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.4%
20x: 95.6%

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: 38 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A4gnt	A	T	9: 99,502,725 (GRCm39)	N295I	probably damaging	Het
Abcg3	G	A	5: 105,116,036 (GRCm39)	A266V	probably damaging	Het
Apbb1	C	A	7: 105,216,922 (GRCm39)	D254Y	probably damaging	Het
Arhgap39	T	C	15: 76,621,618 (GRCm39)	M328V	probably benign	Het
Bub1b	T	A	2: 118,440,325 (GRCm39)	V143D	probably damaging	Het
Celsr3	A	G	9: 108,704,996 (GRCm39)	D493G	probably damaging	Het
Cers4	T	A	8: 4,566,992 (GRCm39)		probably null	Het
Clec4d	A	G	6: 123,251,729 (GRCm39)	R204G	probably benign	Het
Cngb1	C	A	8: 95,980,823 (GRCm39)	R910L	possibly damaging	Het
Coro2a	A	T	4: 46,564,691 (GRCm39)	N18K	probably benign	Het
Cwf19l1	A	G	19: 44,110,380 (GRCm39)	F290S	probably damaging	Het
Esp18	C	T	17: 39,720,839 (GRCm39)	T28I	probably damaging	Het
Hdac10	A	T	15: 89,011,148 (GRCm39)	F205Y	probably benign	Het
Hhip	T	A	8: 80,724,821 (GRCm39)	H317L	possibly damaging	Het
Il36b	G	A	2: 24,044,661 (GRCm39)	M20I	probably benign	Het
Ilf3	T	A	9: 21,306,168 (GRCm39)	N276K	probably damaging	Het
Jchain	T	C	5: 88,670,376 (GRCm39)	N81S	probably benign	Het
Mei4	A	G	9: 81,907,600 (GRCm39)	Y211C	probably damaging	Het
Mx2	A	T	16: 97,339,904 (GRCm39)	E20V	possibly damaging	Het
Ndufa10	A	G	1: 92,388,096 (GRCm39)		probably null	Het
Nodal	A	G	10: 61,259,456 (GRCm39)	T298A	probably damaging	Het
Nvl	T	C	1: 180,966,863 (GRCm39)	Y47C	probably damaging	Het
Onecut1	C	T	9: 74,770,674 (GRCm39)	R366C	probably damaging	Het
Or9q1	T	C	19: 13,804,983 (GRCm39)	Y259C	probably damaging	Het
Plekha6	G	C	1: 133,200,045 (GRCm39)	R208P	possibly damaging	Het
Ppp5c	A	G	7: 16,761,616 (GRCm39)		probably null	Het
Prag1	A	G	8: 36,570,641 (GRCm39)	E408G	probably benign	Het
Ptpn21	T	C	12: 98,648,809 (GRCm39)	N949S	probably damaging	Het
Scn7a	A	C	2: 66,527,912 (GRCm39)	N859K	possibly damaging	Het
Smarca4	T	C	9: 21,597,322 (GRCm39)	I1362T	probably damaging	Het
Syt12	T	C	19: 4,501,022 (GRCm39)	R343G	possibly damaging	Het
Topbp1	T	C	9: 103,200,727 (GRCm39)	S587P	probably benign	Het
Trim80	C	T	11: 115,337,301 (GRCm39)	Q388*	probably null	Het
Vmn2r130	T	A	17: 23,280,461 (GRCm39)	S41T	probably benign	Het
Vmn2r3	T	A	3: 64,166,444 (GRCm39)	T896S	possibly damaging	Het
Xirp2	A	G	2: 67,340,006 (GRCm39)	E749G	probably damaging	Het
Zbtb24	G	A	10: 41,327,849 (GRCm39)	G245E	probably benign	Het
Zfp507	A	G	7: 35,487,167 (GRCm39)	V767A	probably benign	Het

Other mutations in Tsc2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
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'- GAATCAGAGATGGTATAGCCTCGG -3'
(R):5'- TTGCAGTCATCCTCAGCATC -3'

Sequencing Primer
(F):5'- ACTGGAAGGCAGAGGACCTTC -3'
(R):5'- CTAGCCAGGAAGAAAAGTCCCATTTG -3'

Posted On

2016-12-15