Mutagenetix > Incidental Mutation

Incidental Mutation 'R3971:Tsc2'

310995

Institutional Source

Beutler Lab

Gene Symbol

Tsc2

Ensembl Gene

ENSMUSG00000002496

Gene Name

TSC complex subunit 2

Synonyms

tuberin, Nafld, tuberous sclerosis 2

MMRRC Submission

040839-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3971 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

24814790-24851604 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 24842562 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 288 (D288G)

Ref Sequence

ENSEMBL: ENSMUSP00000153792 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000097373
AA Change: D288G

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

SMART Domains

Protein: ENSMUSP00000094986
Gene: ENSMUSG00000002496
AA Change: D288G

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: D288G

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

Predicted Effect

probably damaging
Transcript: ENSMUST00000226398
AA Change: D288G

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000227607
AA Change: D229G

PolyPhen 2 Score 0.952 (Sensitivity: 0.79; Specificity: 0.95)

Predicted Effect

probably damaging
Transcript: ENSMUST00000227745
AA Change: D288G

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227754

Predicted Effect

probably damaging
Transcript: ENSMUST00000228412
AA Change: D288G

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

Meta Mutation Damage Score

0.6894

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.1%
20x: 94.3%

Validation Efficiency

95% (38/40)

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: 40 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aadat	C	T	8: 60,971,615 (GRCm39)	P147L	probably damaging	Het
Apbb1ip	T	A	2: 22,713,506 (GRCm39)	D120E	unknown	Het
Atp10b	A	G	11: 43,107,339 (GRCm39)	D791G	probably damaging	Het
Aunip	A	G	4: 134,250,780 (GRCm39)	K242E	possibly damaging	Het
Ccdc80	A	G	16: 44,916,183 (GRCm39)	E313G	probably benign	Het
Cd72	C	T	4: 43,449,491 (GRCm39)	R275H	probably damaging	Het
Chrnb1	A	G	11: 69,683,742 (GRCm39)		probably benign	Het
Coro2b	C	T	9: 62,336,522 (GRCm39)	A251T	possibly damaging	Het
Cspg4b	A	G	13: 113,453,660 (GRCm39)	E41G	probably damaging	Het
Ddr2	A	G	1: 169,815,986 (GRCm39)	F574L	probably damaging	Het
Dock1	G	A	7: 134,348,637 (GRCm39)	D284N	probably damaging	Het
Dync1h1	A	G	12: 110,632,399 (GRCm39)	H4506R	probably benign	Het
Fam174b	T	C	7: 73,416,348 (GRCm39)	V147A	probably damaging	Het
Glp2r	T	A	11: 67,637,641 (GRCm39)	D130V	possibly damaging	Het
Gm18856	A	T	13: 14,139,433 (GRCm39)		probably benign	Het
Gm7247	A	G	14: 51,602,841 (GRCm39)	Y59C	probably damaging	Het
Hecw1	T	C	13: 14,411,514 (GRCm39)	D1062G	probably damaging	Het
Ifit2	A	G	19: 34,551,441 (GRCm39)	E327G	probably benign	Het
Ighv1-37	A	T	12: 114,860,079 (GRCm39)	S43T	probably damaging	Het
Man2b1	A	G	8: 85,812,020 (GRCm39)	N158S	probably damaging	Het
Mcoln1	T	A	8: 3,557,408 (GRCm39)	I138K	probably benign	Het
Mki67	A	C	7: 135,297,859 (GRCm39)	S2392A	probably benign	Het
Mrc2	G	A	11: 105,218,857 (GRCm39)	D193N	possibly damaging	Het
Myo5b	C	T	18: 74,873,598 (GRCm39)	L1501F	probably damaging	Het
Nckap1l	A	G	15: 103,370,987 (GRCm39)	K189E	probably damaging	Het
Obscn	T	C	11: 59,022,472 (GRCm39)	R758G	possibly damaging	Het
Or6c69	T	C	10: 129,747,742 (GRCm39)	N135S	probably benign	Het
Otop1	A	G	5: 38,457,533 (GRCm39)	I431V	probably benign	Het
Psma8	A	G	18: 14,890,444 (GRCm39)	K195E	possibly damaging	Het
Rbm25	A	G	12: 83,721,982 (GRCm39)	T723A	probably benign	Het
Sema3b	A	G	9: 107,477,567 (GRCm39)	S485P	probably benign	Het
Slc12a2	T	A	18: 58,063,268 (GRCm39)	L916Q	possibly damaging	Het
Spata31d1a	T	A	13: 59,849,971 (GRCm39)	D719V	possibly damaging	Het
Synj1	A	G	16: 90,788,491 (GRCm39)	S86P	probably damaging	Het
Tmem130	T	A	5: 144,692,131 (GRCm39)	H91L	probably benign	Het
Ttn	A	T	2: 76,641,587 (GRCm39)	L5176Q	possibly damaging	Het
Vps35l	T	C	7: 118,433,022 (GRCm39)	I585T	probably damaging	Het
Wac	T	C	18: 7,916,175 (GRCm39)	V303A	probably damaging	Het
Zfhx2	A	G	14: 55,311,932 (GRCm39)	V254A	probably benign	Het
Zfp993	A	G	4: 146,742,089 (GRCm39)	T138A	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
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'- TGGGCAAACCTGATGCAAGC -3'
(R):5'- CCCATGTGACCAGTAGTGAC -3'

Sequencing Primer
(F):5'- ACCTGATGCAAGCTCTCCC -3'
(R):5'- AATCACAGTTGCTGCTGGC -3'

Posted On

2015-04-29