Mutagenetix > Incidental Mutation

Incidental Mutation 'R4906:Tsc1'

500815

Institutional Source

Beutler Lab

Gene Symbol

Tsc1

Ensembl Gene

ENSMUSG00000026812

Gene Name

TSC complex subunit 1

Synonyms

tuberous sclerosis 1, hamartin

MMRRC Submission

042508-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4906 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

28531240-28581179 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 28565201 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Glycine at position 421 (E421G)

Ref Sequence

ENSEMBL: ENSMUSP00000109501 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028155] [ENSMUST00000113867] [ENSMUST00000113869] [ENSMUST00000113870] [ENSMUST00000133565] [ENSMUST00000156857]

AlphaFold

Q9EP53

Predicted Effect

possibly damaging
Transcript: ENSMUST00000028155
AA Change: E421G

PolyPhen 2 Score 0.807 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000028155
Gene: ENSMUSG00000026812
AA Change: E421G

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: E421G

PolyPhen 2 Score 0.663 (Sensitivity: 0.86; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000109498
Gene: ENSMUSG00000026812
AA Change: E421G

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: E422G

PolyPhen 2 Score 0.711 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000109500
Gene: ENSMUSG00000026812
AA Change: E422G

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

possibly damaging
Transcript: ENSMUST00000113870
AA Change: E421G

PolyPhen 2 Score 0.807 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000109501
Gene: ENSMUSG00000026812
AA Change: E421G

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

noncoding transcript
Transcript: ENSMUST00000125715

Predicted Effect

possibly damaging
Transcript: ENSMUST00000133565
AA Change: E422G

PolyPhen 2 Score 0.785 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000120888
Gene: ENSMUSG00000026812
AA Change: E422G

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000139642

Predicted Effect

probably benign
Transcript: ENSMUST00000156857

SMART Domains

Protein: ENSMUSP00000115380
Gene: ENSMUSG00000026812

Domain	Start	End	E-Value	Type
Pfam:Hamartin	2	348	2.3e-170	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153625

Coding Region Coverage

1x: 98.9%
3x: 98.1%
10x: 95.7%
20x: 90.5%

Validation Efficiency

MGI Phenotype

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: 91 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
5330417H12Rik	T	C	7: 107,223,897 (GRCm39)		probably benign	Het
Ablim2	C	T	5: 35,959,766 (GRCm39)	R73C	possibly damaging	Het
Adgrf2	T	C	17: 43,022,084 (GRCm39)	I247V	probably benign	Het
Adgrv1	A	G	13: 81,418,857 (GRCm39)		probably null	Het
Ankrd22	T	A	19: 34,126,752 (GRCm39)	K26I	possibly damaging	Het
Arhgap32	T	A	9: 32,156,552 (GRCm39)		probably null	Het
Armc10	A	G	5: 21,866,522 (GRCm39)	Y262C	probably damaging	Het
Arrb2	A	G	11: 70,330,725 (GRCm39)	D374G	probably benign	Het
Ascc3	C	T	10: 50,625,227 (GRCm39)	R1675C	probably damaging	Het
Atg5	T	C	10: 44,239,046 (GRCm39)	*276R	probably null	Het
Bcl11b	G	A	12: 107,882,968 (GRCm39)	T377M	probably damaging	Het
C1s2	C	A	6: 124,612,073 (GRCm39)	E104*	probably null	Het
Carf	A	T	1: 60,180,526 (GRCm39)	H316L	probably damaging	Het
Ccdc77	A	T	6: 120,311,796 (GRCm39)	I234N	probably damaging	Het
Cd300c2	A	T	11: 114,887,826 (GRCm39)	V192E	possibly damaging	Het
Cep72	G	A	13: 74,207,584 (GRCm39)	R62C	probably damaging	Het
Clasp1	T	A	1: 118,436,640 (GRCm39)	L308*	probably null	Het
Clec2g	A	G	6: 128,956,411 (GRCm39)	S25G	probably benign	Het
Cngb1	T	C	8: 95,978,601 (GRCm39)	M1046V	probably damaging	Het
Cobll1	A	T	2: 64,928,037 (GRCm39)	D1095E	probably benign	Het
Cpeb2	A	G	5: 43,402,005 (GRCm39)	H662R	possibly damaging	Het
Cps1	A	T	1: 67,178,922 (GRCm39)	T45S	probably benign	Het
Cspp1	A	G	1: 10,152,553 (GRCm39)	Q368R	possibly damaging	Het
Dcaf6	C	A	1: 165,239,032 (GRCm39)		probably null	Het
Dcst1	T	C	3: 89,257,814 (GRCm39)	Y652C	possibly damaging	Het
Elf5	T	G	2: 103,279,918 (GRCm39)	Y225*	probably null	Het
Ermap	A	C	4: 119,046,015 (GRCm39)		probably benign	Het
Fam186b	A	T	15: 99,169,202 (GRCm39)	V915D	probably damaging	Het
Fbxo34	C	A	14: 47,766,911 (GRCm39)	N90K	probably benign	Het
Flnc	A	G	6: 29,447,524 (GRCm39)	E1109G	probably damaging	Het
Flt1	C	A	5: 147,620,749 (GRCm39)	A132S	probably benign	Het
Gabpb2	A	G	3: 95,097,947 (GRCm39)	V242A	probably benign	Het
Gas2l3	CACTCGTCATACT	CACT	10: 89,266,820 (GRCm39)		probably benign	Het
Gm21798	A	T	15: 64,689,732 (GRCm39)		probably benign	Het
Gpr179	A	T	11: 97,237,487 (GRCm39)	S345T	possibly damaging	Het
Gusb	A	T	5: 130,026,959 (GRCm39)	F377L	probably damaging	Het
Hnrnpu	T	C	1: 178,156,938 (GRCm39)		probably benign	Het
Htr3b	C	T	9: 48,848,348 (GRCm39)		probably null	Het
Iqub	A	T	6: 24,501,368 (GRCm39)	V194D	probably damaging	Het
Itga2b	A	G	11: 102,351,985 (GRCm39)	V504A	probably benign	Het
Itga4	T	A	2: 79,118,592 (GRCm39)	F430L	probably damaging	Het
Jcad	C	A	18: 4,673,762 (GRCm39)	P508H	probably damaging	Het
Jph1	T	C	1: 17,161,835 (GRCm39)	T276A	probably damaging	Het
Kansl2	A	G	15: 98,429,771 (GRCm39)	F87S	possibly damaging	Het
Kdm1b	T	C	13: 47,216,620 (GRCm39)		probably null	Het
Kif5b	C	T	18: 6,220,930 (GRCm39)	D393N	probably benign	Het
Kmt2d	A	T	15: 98,747,420 (GRCm39)		probably benign	Het
Krt75	A	G	15: 101,478,674 (GRCm39)	I320T	probably damaging	Het
Lhfpl7	T	A	5: 113,386,036 (GRCm39)	M161K	probably benign	Het
Lipo5	T	C	19: 33,443,348 (GRCm39)	N156S	unknown	Het
Mblac2	A	C	13: 81,859,706 (GRCm39)	Q19P	probably null	Het
Mdfic2	A	T	6: 98,215,080 (GRCm39)	M181K	probably damaging	Het
Mfsd4b3-ps	T	C	10: 39,824,056 (GRCm39)	H68R	probably damaging	Het
Mzb1	A	T	18: 35,781,006 (GRCm39)		probably null	Het
Nup210l	T	A	3: 90,077,337 (GRCm39)	I891N	probably benign	Het
Nwd1	G	A	8: 73,398,841 (GRCm39)	R667Q	probably damaging	Het
Oas1h	C	T	5: 121,005,172 (GRCm39)	Q207*	probably null	Het
Or13c7d	A	T	4: 43,770,476 (GRCm39)	F178L	possibly damaging	Het
Pcdh15	C	T	10: 74,340,625 (GRCm39)	R1120*	probably null	Het
Pfkl	A	G	10: 77,824,144 (GRCm39)	L748P	probably damaging	Het
Phldb2	T	A	16: 45,571,758 (GRCm39)	K473N	probably damaging	Het
Rapgef6	G	A	11: 54,443,662 (GRCm39)	V82I	probably damaging	Het
Rfc3	A	T	5: 151,570,960 (GRCm39)	L112Q	probably damaging	Het
Rsph6a	T	A	7: 18,801,997 (GRCm39)	C349S	possibly damaging	Het
Sec16a	A	T	2: 26,331,979 (GRCm39)		probably benign	Het
Septin14	T	A	5: 129,770,030 (GRCm39)	Y222F	probably benign	Het
Skor2	T	C	18: 76,947,990 (GRCm39)	S571P	possibly damaging	Het
Slc13a5	T	A	11: 72,148,244 (GRCm39)	M264L	probably damaging	Het
Slc45a3	T	A	1: 131,909,315 (GRCm39)	V504E	probably damaging	Het
Smg1	C	T	7: 117,751,631 (GRCm39)		probably benign	Het
Smim20	A	G	5: 53,434,503 (GRCm39)	N45S	probably null	Het
Spp2	A	T	1: 88,339,991 (GRCm39)	S111C	probably damaging	Het
Sspo	A	G	6: 48,442,664 (GRCm39)		probably null	Het
Sycp2	C	T	2: 178,045,450 (GRCm39)		probably null	Het
Tas2r113	A	G	6: 132,870,521 (GRCm39)	N183S	possibly damaging	Het
Tcaf2	A	T	6: 42,606,679 (GRCm39)	M425K	probably benign	Het
Tdrp	A	G	8: 14,003,845 (GRCm39)	V164A	possibly damaging	Het
Tmbim1	A	G	1: 74,328,568 (GRCm39)	F298S	probably damaging	Het
Tmem89	A	G	9: 108,743,829 (GRCm39)		probably benign	Het
Trpm2	G	T	10: 77,768,023 (GRCm39)	C825*	probably null	Het
Usp24	T	C	4: 106,245,834 (GRCm39)	I1364T	probably benign	Het
Vmn1r52	G	A	6: 90,155,930 (GRCm39)	G78E	possibly damaging	Het
Vmn2r73	T	G	7: 85,506,829 (GRCm39)	I828L	probably damaging	Het
Vwa5b1	A	T	4: 138,338,058 (GRCm39)	D87E	probably benign	Het
Zfp1010	T	C	2: 176,957,223 (GRCm39)	T92A	possibly damaging	Het
Zfp451	A	T	1: 33,844,465 (GRCm39)	D47E	probably damaging	Het
Zfp821	A	G	8: 110,450,841 (GRCm39)	E278G	probably damaging	Het
Zfp930	A	T	8: 69,681,597 (GRCm39)	T430S	probably benign	Het
Zfp994	G	T	17: 22,419,448 (GRCm39)	Y500*	probably null	Het
Zmat3	A	T	3: 32,397,836 (GRCm39)	I142N	probably damaging	Het
Zzef1	T	A	11: 72,792,214 (GRCm39)	I2266N	probably damaging	Het

Other mutations in Tsc1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00333:Tsc1	APN	2	28,551,623 (GRCm39)	missense	probably damaging	0.98
IGL00770:Tsc1	APN	2	28,555,023 (GRCm39)	missense	probably damaging	1.00
IGL00774:Tsc1	APN	2	28,555,023 (GRCm39)	missense	probably damaging	1.00
IGL00835:Tsc1	APN	2	28,562,478 (GRCm39)	missense	possibly damaging	0.93
IGL00971:Tsc1	APN	2	28,560,952 (GRCm39)	nonsense	probably null
IGL01808:Tsc1	APN	2	28,552,519 (GRCm39)	missense	probably damaging	1.00
IGL02281:Tsc1	APN	2	28,553,607 (GRCm39)	missense	probably damaging	1.00
IGL03068:Tsc1	APN	2	28,571,270 (GRCm39)	missense	probably damaging	1.00
Cassava	UTSW	2	28,561,898 (GRCm39)	splice site	probably null
R0077:Tsc1	UTSW	2	28,568,955 (GRCm39)	splice site	probably benign
R0149:Tsc1	UTSW	2	28,560,913 (GRCm39)	missense	probably damaging	0.99
R0605:Tsc1	UTSW	2	28,561,790 (GRCm39)	missense	probably damaging	1.00
R0737:Tsc1	UTSW	2	28,560,942 (GRCm39)	missense	possibly damaging	0.94
R1199:Tsc1	UTSW	2	28,555,638 (GRCm39)	missense	probably damaging	1.00
R1751:Tsc1	UTSW	2	28,566,038 (GRCm39)	missense	probably damaging	0.97
R1757:Tsc1	UTSW	2	28,576,125 (GRCm39)	missense	probably benign	0.05
R1807:Tsc1	UTSW	2	28,576,125 (GRCm39)	missense	probably benign	0.05
R2014:Tsc1	UTSW	2	28,555,649 (GRCm39)	splice site	probably benign
R2284:Tsc1	UTSW	2	28,555,109 (GRCm39)	missense	possibly damaging	0.85
R3786:Tsc1	UTSW	2	28,577,154 (GRCm39)	missense	probably damaging	1.00
R4490:Tsc1	UTSW	2	28,560,937 (GRCm39)	missense	probably damaging	0.97
R4707:Tsc1	UTSW	2	28,562,419 (GRCm39)	missense	probably damaging	1.00
R4751:Tsc1	UTSW	2	28,569,093 (GRCm39)	missense	probably damaging	0.96
R4794:Tsc1	UTSW	2	28,551,702 (GRCm39)	splice site	probably null
R5020:Tsc1	UTSW	2	28,566,531 (GRCm39)	missense	probably damaging	1.00
R5401:Tsc1	UTSW	2	28,576,920 (GRCm39)	nonsense	probably null
R5708:Tsc1	UTSW	2	28,555,197 (GRCm39)	intron	probably benign
R6435:Tsc1	UTSW	2	28,566,464 (GRCm39)	missense	probably benign	0.08
R6469:Tsc1	UTSW	2	28,561,898 (GRCm39)	splice site	probably null
R6502:Tsc1	UTSW	2	28,555,613 (GRCm39)	missense	probably damaging	1.00
R6617:Tsc1	UTSW	2	28,577,001 (GRCm39)	missense	possibly damaging	0.82
R7098:Tsc1	UTSW	2	28,565,744 (GRCm39)	missense	probably benign	0.00
R7503:Tsc1	UTSW	2	28,577,088 (GRCm39)	missense	possibly damaging	0.50
R7608:Tsc1	UTSW	2	28,548,748 (GRCm39)	missense	probably benign	0.01
R7677:Tsc1	UTSW	2	28,562,829 (GRCm39)	missense	probably benign	0.11
R7791:Tsc1	UTSW	2	28,571,960 (GRCm39)	missense	probably damaging	1.00
R8021:Tsc1	UTSW	2	28,576,901 (GRCm39)	missense	possibly damaging	0.67
R8203:Tsc1	UTSW	2	28,563,007 (GRCm39)	splice site	probably null
R8228:Tsc1	UTSW	2	28,566,141 (GRCm39)	missense	probably benign	0.23
R9057:Tsc1	UTSW	2	28,575,874 (GRCm39)	missense	probably damaging	1.00
R9088:Tsc1	UTSW	2	28,552,617 (GRCm39)	missense	possibly damaging	0.94
R9201:Tsc1	UTSW	2	28,576,791 (GRCm39)	missense	probably benign
R9386:Tsc1	UTSW	2	28,561,858 (GRCm39)	missense	probably benign
R9731:Tsc1	UTSW	2	28,566,486 (GRCm39)	missense	probably benign	0.00
R9780:Tsc1	UTSW	2	28,565,761 (GRCm39)	missense	probably damaging	0.98

Predicted Primers

PCR Primer
(F):5'- ATGGGCCTGACACACCAAAG -3'
(R):5'- AATACTGGTGTTTCATACCCCTGG -3'

Sequencing Primer
(F):5'- GTCCCATAGACCCACCCTCAG -3'
(R):5'- GTTTCATACCCCTGGGAGTCAG -3'

Posted On

2017-12-01