Mutagenetix > Incidental Mutations

Incidental Mutation 'R4751:Tsc1'

357546

Institutional Source

Beutler Lab

Gene Symbol

Tsc1

Ensembl Gene

ENSMUSG00000026812

Gene Name

tuberous sclerosis 1

Synonyms

hamartin

MMRRC Submission

041970-MU

Accession Numbers

Ncbi RefSeq: NM_022887.3; MGI: 1929183

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4751 (G1)

Quality Score

216

Status

Validated

Chromosome

Chromosomal Location

28641228-28691167 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 28679081 bp

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 720 (I720N)

Ref Sequence

ENSEMBL: ENSMUSP00000109501 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028155] [ENSMUST00000113867] [ENSMUST00000113869] [ENSMUST00000113870] [ENSMUST00000133565]

Predicted Effect

probably damaging
Transcript: ENSMUST00000028155
AA Change: I720N

PolyPhen 2 Score 0.965 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000028155
Gene: ENSMUSG00000026812
AA Change: I720N

Domain	Start	End	E-Value	Type
Pfam:Hamartin	2	715	2.2e-281	PFAM
SCOP:d1eq1a_	723	886	4e-11	SMART
low complexity region	974	990	N/A	INTRINSIC
low complexity region	1025	1042	N/A	INTRINSIC
low complexity region	1099	1117	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000113867
AA Change: I715N

PolyPhen 2 Score 0.892 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000109498
Gene: ENSMUSG00000026812
AA Change: I715N

Domain	Start	End	E-Value	Type
Pfam:Hamartin	2	710	7.3e-279	PFAM
SCOP:d1eq1a_	718	881	6e-11	SMART
low complexity region	969	985	N/A	INTRINSIC
low complexity region	1020	1037	N/A	INTRINSIC
low complexity region	1094	1112	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000113869
AA Change: I721N

PolyPhen 2 Score 0.827 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000109500
Gene: ENSMUSG00000026812
AA Change: I721N

Domain	Start	End	E-Value	Type
Pfam:Hamartin	7	716	6e-279	PFAM
SCOP:d1eq1a_	724	887	4e-11	SMART
low complexity region	975	991	N/A	INTRINSIC
low complexity region	1026	1043	N/A	INTRINSIC
low complexity region	1100	1118	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000113870
AA Change: I720N

PolyPhen 2 Score 0.965 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000109501
Gene: ENSMUSG00000026812
AA Change: I720N

Domain	Start	End	E-Value	Type
Pfam:Hamartin	2	715	2.2e-281	PFAM
SCOP:d1eq1a_	723	886	4e-11	SMART
low complexity region	974	990	N/A	INTRINSIC
low complexity region	1025	1042	N/A	INTRINSIC
low complexity region	1099	1117	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000133565

SMART Domains

Protein: ENSMUSP00000120888
Gene: ENSMUSG00000026812

Domain	Start	End	E-Value	Type
Pfam:Hamartin	2	455	1.3e-198	PFAM

Meta Mutation Damage Score

0.4300

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.4%

Validation Efficiency

95% (124/131)

MGI Phenotype

Strain: 2183900
Lethality: E10-E12
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a growth inhibitory protein thought to play a role in the stabilization of tuberin. Mutations in this gene have been associated with tuberous sclerosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]
PHENOTYPE: Homozygous null mutants show liver hypoplasia, open neural tube and die by embryonic day 10.5-11.5. Heterozygotes develop kidney cystadenomas and liver hemangiomas. Conditional astrocyte-specific nulls show increased astrocyte numbers and seizures. [provided by MGI curators]

Allele List at MGI

All alleles(38) : Targeted(7) Gene trapped(31)

Other mutations in this stock

Total: 115 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9130023H24Rik	A	T	7: 128,237,086	C112S	probably benign	Het
Abca13	G	A	11: 9,277,973		probably null	Het
Abca14	A	G	7: 120,312,177	E1328G	probably benign	Het
Abca9	T	A	11: 110,130,570	I1105F	probably benign	Het
Abr	T	C	11: 76,456,608	N396D	possibly damaging	Het
Aftph	A	C	11: 20,727,074	C178W	probably damaging	Het
Akr1c14	T	C	13: 4,065,338	F89S	possibly damaging	Het
Ank3	C	T	10: 69,986,206	A1518V	probably benign	Het
Arfgap2	T	G	2: 91,267,368	S143R	probably benign	Het
Aspdh	T	A	7: 44,467,205	C107*	probably null	Het
Asphd2	C	A	5: 112,391,746	G74W	probably damaging	Het
AU040320	G	A	4: 126,854,466		probably null	Het
B3glct	T	A	5: 149,725,402		probably null	Het
Bcl9l	A	G	9: 44,506,803	K646R	probably damaging	Het
Brat1	T	G	5: 140,718,296	L768R	probably damaging	Het
Btbd18	T	A	2: 84,667,921	Y634*	probably null	Het
Bub1	T	A	2: 127,823,938		probably benign	Het
Carns1	A	T	19: 4,166,418	D588E	probably damaging	Het
Cast	T	C	13: 74,746,047	K141E	probably damaging	Het
Cd109	CATTTATTTATTTATTTATTTATTTATTTATTTAT	CATTTATTTATTTATTTATTTATTTATTTATTTATTTAT	9: 78,712,500		probably benign	Het
Chsy3	T	C	18: 59,175,800	S42P	possibly damaging	Het
Clca1	A	T	3: 145,004,848	F865I	possibly damaging	Het
Clec4f	T	A	6: 83,645,282	M526L	possibly damaging	Het
Clnk	T	C	5: 38,720,913	E301G	probably benign	Het
Colgalt2	T	A	1: 152,489,876	I309N	probably benign	Het
Cyp2e1	A	T	7: 140,774,716	K326*	probably null	Het
Dagla	T	A	19: 10,250,394	T717S	probably benign	Het
Dnajc11	G	A	4: 151,968,542	R141H	probably benign	Het
Dst	A	G	1: 34,191,884	K2853E	probably benign	Het
Eif4g1	A	G	16: 20,686,515	K1208E	possibly damaging	Het
Elane	A	G	10: 79,886,791	R48G	probably benign	Het
Fbxo30	T	A	10: 11,290,195	N220K	probably benign	Het
Fbxo33	A	T	12: 59,200,928		probably benign	Het
Fetub	G	A	16: 22,937,895	V169I	probably benign	Het
Gm13762	A	G	2: 88,973,133	C253R	probably damaging	Het
Gm5861	T	A	5: 11,186,491	Y138N	probably damaging	Het
Gpx6	A	C	13: 21,317,064	Q107H	probably damaging	Het
Hist2h2bb	A	T	3: 96,269,151		probably benign	Het
Homer3	A	T	8: 70,285,434	I19F	probably damaging	Het
Hspa4	C	T	11: 53,284,199	V144I	probably benign	Het
Icos	C	T	1: 60,993,717	S25L	probably benign	Het
Ifna4	A	G	4: 88,841,948	T30A	probably benign	Het
Ino80b	C	T	6: 83,124,750	G46D	probably damaging	Het
Kpna2	T	G	11: 106,992,664	I100L	possibly damaging	Het
Krt71	C	T	15: 101,735,466	G446R	probably damaging	Het
Krtap31-2	A	G	11: 99,936,576	N78S	possibly damaging	Het
Lman1	A	G	18: 65,998,434	S132P	probably benign	Het
Lmna	T	C	3: 88,486,533	Q246R	possibly damaging	Het
Lrp10	T	A	14: 54,468,592	V413E	probably damaging	Het
Macf1	A	C	4: 123,471,650	I1541S	probably benign	Het
Med24	A	G	11: 98,706,432	L874P	probably damaging	Het
Mgll	T	A	6: 88,725,111		probably benign	Het
Mrpl37	A	T	4: 107,057,475	L364Q	probably damaging	Het
Mrpl47	C	T	3: 32,728,441	R209H	probably benign	Het
Muc5ac	T	C	7: 141,817,601	F3285L	probably benign	Het
Mylk	A	G	16: 34,879,169	R301G	probably benign	Het
Nacad	A	G	11: 6,605,726	L8P	unknown	Het
Ncf1	T	A	5: 134,229,545	H8L	probably damaging	Het
Ncoa3	T	A	2: 166,069,903	M1383K	possibly damaging	Het
Necab2	C	T	8: 119,467,598	S271L	probably benign	Het
Nme8	A	T	13: 19,675,638		probably null	Het
Nsrp1	T	G	11: 77,076,719	T16P	possibly damaging	Het
Obox3	A	T	7: 15,625,692		probably null	Het
Olfr1211	T	A	2: 88,929,914	I134F	probably damaging	Het
Olfr1416	C	A	1: 92,479,983	A213S	probably benign	Het
Olfr1428	T	A	19: 12,109,177	Y123F	probably damaging	Het
Olfr355	T	C	2: 36,927,583	H177R	probably damaging	Het
Olfr667	A	T	7: 104,916,410	Y295*	probably null	Het
Osbpl3	C	G	6: 50,300,997	E790Q	possibly damaging	Het
Osmr	A	T	15: 6,842,852	W254R	probably damaging	Het
Otoa	T	C	7: 121,132,924		probably benign	Het
Pagr1a	A	T	7: 127,015,379	L218H	probably damaging	Het
Pcdha11	G	A	18: 37,006,944	G542D	probably damaging	Het
Pck2	T	A	14: 55,542,561	I54N	probably damaging	Het
Ppif	T	C	14: 25,699,499	V173A	probably damaging	Het
Ptgs2	T	A	1: 150,104,020	L292H	probably damaging	Het
Ptpru	A	G	4: 131,802,586	S604P	probably damaging	Het
Qrfpr	T	C	3: 36,182,622	H210R	possibly damaging	Het
Rasgrf1	A	G	9: 89,910,118	T41A	probably damaging	Het
Rasgrf1	A	G	9: 90,012,866	H1113R	probably damaging	Het
Rhoc	T	A	3: 104,792,647	I80N	probably damaging	Het
Riok3	A	G	18: 12,153,983	N472S	probably benign	Het
Rnf213	A	G	11: 119,445,745	Y3314C	probably benign	Het
Shank2	C	T	7: 144,409,468	T264I	probably damaging	Het
Shroom3	G	T	5: 92,943,086	V1151F	probably damaging	Het
Sipa1l1	A	G	12: 82,341,194	I65V	probably benign	Het
Slc22a19	T	C	19: 7,691,145	K291R	possibly damaging	Het
Slc22a20	T	C	19: 5,980,460	I315V	probably benign	Het
Slc44a1	A	T	4: 53,560,973	D563V	probably damaging	Het
Smchd1	A	T	17: 71,391,468	H1104Q	probably benign	Het
Spcs2	A	T	7: 99,844,769		probably null	Het
Sptb	T	C	12: 76,627,110	E301G	probably benign	Het
Stum	T	C	1: 180,442,669	D86G	probably damaging	Het
Sufu	A	T	19: 46,483,649	D449V	probably benign	Het
Sun5	T	C	2: 153,866,016		probably null	Het
Tbc1d15	T	A	10: 115,202,587	I574F	probably damaging	Het
Tert	G	A	13: 73,628,063	S311N	possibly damaging	Het
Tiparp	T	C	3: 65,552,804	Y507H	probably damaging	Het
Tnk2	T	C	16: 32,679,857	C158R	probably damaging	Het
Tpgs1	T	C	10: 79,675,620	S199P	possibly damaging	Het
Trdmt1	G	T	2: 13,544,653		probably benign	Het
Trp53bp1	T	A	2: 121,227,809	D944V	probably damaging	Het
Ttn	T	C	2: 76,709,605	T34346A	probably benign	Het
Ttn	T	C	2: 76,897,581		probably benign	Het
Uba7	T	A	9: 107,979,805	C686S	possibly damaging	Het
Ush2a	T	A	1: 188,850,087	F3782L	probably damaging	Het
Vars2	A	T	17: 35,659,343	H745Q	possibly damaging	Het
Vgf	T	A	5: 137,032,401	D472E	probably damaging	Het
Vmn2r15	T	C	5: 109,286,754	M695V	probably benign	Het
Vps41	A	T	13: 18,811,622	D208V	probably damaging	Het
Vta1	C	T	10: 14,655,816	A272T	probably benign	Het
Wnk4	G	A	11: 101,276,362		probably benign	Het
Zfp507	T	C	7: 35,794,382	K412R	probably damaging	Het
Zfp768	A	G	7: 127,344,762	F65L	possibly damaging	Het
Zfp956	T	C	6: 47,963,576	S290P	probably benign	Het

Other mutations in Tsc1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00333:Tsc1	APN	2	28661611	missense	probably damaging	0.98
IGL00770:Tsc1	APN	2	28665011	missense	probably damaging	1.00
IGL00774:Tsc1	APN	2	28665011	missense	probably damaging	1.00
IGL00835:Tsc1	APN	2	28672466	missense	possibly damaging	0.93
IGL00971:Tsc1	APN	2	28670940	nonsense	probably null
IGL01808:Tsc1	APN	2	28662507	missense	probably damaging	1.00
IGL02281:Tsc1	APN	2	28663595	missense	probably damaging	1.00
IGL03068:Tsc1	APN	2	28681258	missense	probably damaging	1.00
Cassava	UTSW	2	28671886	splice site	probably null
R0077:Tsc1	UTSW	2	28678943	splice site	probably benign
R0149:Tsc1	UTSW	2	28670901	missense	probably damaging	0.99
R0605:Tsc1	UTSW	2	28671778	missense	probably damaging	1.00
R0737:Tsc1	UTSW	2	28670930	missense	possibly damaging	0.94
R1199:Tsc1	UTSW	2	28665626	missense	probably damaging	1.00
R1751:Tsc1	UTSW	2	28676026	missense	probably damaging	0.97
R1757:Tsc1	UTSW	2	28686113	missense	probably benign	0.05
R1807:Tsc1	UTSW	2	28686113	missense	probably benign	0.05
R2014:Tsc1	UTSW	2	28665637	splice site	probably benign
R2284:Tsc1	UTSW	2	28665097	missense	possibly damaging	0.85
R3786:Tsc1	UTSW	2	28687142	missense	probably damaging	1.00
R4490:Tsc1	UTSW	2	28670925	missense	probably damaging	0.97
R4707:Tsc1	UTSW	2	28672407	missense	probably damaging	1.00
R4794:Tsc1	UTSW	2	28661690	splice site	probably null
R4906:Tsc1	UTSW	2	28675189	missense	possibly damaging	0.81
R5020:Tsc1	UTSW	2	28676519	missense	probably damaging	1.00
R5401:Tsc1	UTSW	2	28686908	nonsense	probably null
R5708:Tsc1	UTSW	2	28665185	intron	probably benign
R6435:Tsc1	UTSW	2	28676452	missense	probably benign	0.08
R6469:Tsc1	UTSW	2	28671886	splice site	probably null
R6502:Tsc1	UTSW	2	28665601	missense	probably damaging	1.00
R6617:Tsc1	UTSW	2	28686989	missense	possibly damaging	0.82
R7098:Tsc1	UTSW	2	28675732	missense	probably benign	0.00
R7503:Tsc1	UTSW	2	28687076	missense	possibly damaging	0.50
R7608:Tsc1	UTSW	2	28658736	missense	probably benign	0.01
R7677:Tsc1	UTSW	2	28672817	missense	probably benign	0.11

Predicted Primers

PCR Primer
(F):5'- TGTAAATAGCCTTTCTGCCACC -3'
(R):5'- TTCCGCAATGCCAAGCAGTC -3'

Sequencing Primer
(F):5'- ACCTTCCCTCTGCTTTAAAATCAGG -3'
(R):5'- GAGAAGTTATGAGATTTAGCCATGC -3'

Posted On

2015-11-11