Mutagenetix > Incidental Mutations

Incidental Mutation 'R7503:Tsc1'

581600

Institutional Source

Beutler Lab

Gene Symbol

Tsc1

Ensembl Gene

ENSMUSG00000026812

Gene Name

tuberous sclerosis 1

Synonyms

hamartin

MMRRC Submission

Accession Numbers

Ncbi RefSeq: NM_022887.3; MGI: 1929183

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R7503 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

28641228-28691167 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 28687076 bp

Zygosity

Heterozygous

Amino Acid Change

Leucine to Glutamine at position 1130 (L1130Q)

Ref Sequence

ENSEMBL: ENSMUSP00000109500 (fasta)

Gene Model

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000028155
AA Change: L1129Q

PolyPhen 2 Score 0.795 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000028155
Gene: ENSMUSG00000026812
AA Change: L1129Q

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: L1124Q

PolyPhen 2 Score 0.795 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000109498
Gene: ENSMUSG00000026812
AA Change: L1124Q

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: L1130Q

PolyPhen 2 Score 0.499 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000109500
Gene: ENSMUSG00000026812
AA Change: L1130Q

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: L1129Q

PolyPhen 2 Score 0.795 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000109501
Gene: ENSMUSG00000026812
AA Change: L1129Q

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

0.0858

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.8%

Validation Efficiency

100% (63/63)

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
5730559C18Rik	T	C	1: 136,215,937	D587G	possibly damaging	Het
A230072I06Rik	G	A	8: 12,279,554	G3D	unknown	Het
Aif1	A	T	17: 35,171,573	I67N	probably damaging	Het
Akap11	T	C	14: 78,512,001	D982G		Het
Anpep	A	G	7: 79,826,637	L827P	probably damaging	Het
Arhgef5	A	T	6: 43,273,999	K561N	probably benign	Het
Arsj	T	C	3: 126,364,844	F24S	probably benign	Het
Bard1	T	C	1: 71,030,836	D661G	probably damaging	Het
Cc2d2b	A	G	19: 40,794,612	I618V	unknown	Het
Cfap54	T	A	10: 92,887,436		probably null	Het
Cfhr2	T	A	1: 139,831,214	I33F	probably damaging	Het
Dsc1	G	A	18: 20,085,865	H827Y	probably damaging	Het
Eif3i	C	T	4: 129,600,414	D31N	probably damaging	Het
Eno1b	A	T	18: 48,046,811	T19S	probably damaging	Het
Eva1a	G	A	6: 82,071,229	W29*	probably null	Het
Evc	T	C	5: 37,300,767	K803R	unknown	Het
F5	T	A	1: 164,192,210	N751K	probably damaging	Het
Fam120a	A	T	13: 48,949,247	N177K	probably benign	Het
Farp2	T	G	1: 93,567,497	I164R	probably benign	Het
Gm20379	C	T	13: 92,306,057	P26L		Het
Gm4778	A	T	3: 94,266,473	M259L	probably benign	Het
Hmgcs2	T	C	3: 98,302,624	S433P	probably damaging	Het
Ints2	T	C	11: 86,232,055	T633A	probably benign	Het
Invs	C	T	4: 48,396,347	T340M	probably damaging	Het
Mef2c	A	C	13: 83,662,504	D391A	possibly damaging	Het
Msh4	A	C	3: 153,867,750	S756A	probably damaging	Het
Mylk3	T	C	8: 85,353,589	T490A	probably benign	Het
Myo1b	A	T	1: 51,776,602		probably null	Het
Nsmce1	A	G	7: 125,471,934	S107P	probably benign	Het
Olfr1173	T	C	2: 88,274,695	Y118C	probably damaging	Het
Olfr628	T	A	7: 103,732,267	S114T	probably damaging	Het
Pcdhb21	G	A	18: 37,514,975	D386N	probably benign	Het
Pcdhb22	T	G	18: 37,519,102	L208V	probably benign	Het
Pigu	C	T	2: 155,331,144		probably null	Het
Plcz1	T	A	6: 139,990,748	E585V	probably damaging	Het
Pnpla7	C	A	2: 24,983,532	C183*	probably null	Het
Pomgnt1	T	C	4: 116,152,752	V133A	possibly damaging	Het
Prl3d3	A	G	13: 27,161,113	Y156C	probably benign	Het
Prpf39	A	G	12: 65,053,393	D280G	probably benign	Het
Recql5	C	A	11: 115,895,055	A631S	probably benign	Het
Runx3	C	A	4: 135,155,368	N138K	probably damaging	Het
Scaper	T	C	9: 55,807,754	D750G	probably damaging	Het
Slc16a3	T	C	11: 120,957,027	L347P	probably damaging	Het
Slc25a1	G	T	16: 17,926,439	Y209*	probably null	Het
Smad2	A	G	18: 76,286,885	S88G	probably benign	Het
Sorcs1	A	G	19: 50,153,052	C1125R	probably benign	Het
Spata21	T	A	4: 141,095,303	I140N	probably benign	Het
Speer3	A	T	5: 13,793,334	D85V	probably benign	Het
Stra6	A	G	9: 58,151,245	N463S	possibly damaging	Het
Tmem14a	T	G	1: 21,229,399		probably null	Het
Ttn	T	C	2: 76,781,057	D17377G	possibly damaging	Het
Utf1	A	G	7: 139,944,133	D87G	probably damaging	Het
Vmn2r6	G	A	3: 64,539,951	Q565*	probably null	Het
Vmn2r63	A	T	7: 42,933,590	M67K	probably benign	Het
Vmn2r90	T	C	17: 17,713,248	Y357H	not run	Het
Vmn2r97	A	G	17: 18,928,208	T122A	probably benign	Het
Wdhd1	T	C	14: 47,250,791	E753G	probably benign	Het
Wdr11	A	G	7: 129,603,110	N213S	probably benign	Het
Wdr66	G	T	5: 123,297,458	E994*	probably null	Het
Xdh	A	C	17: 73,926,210	D207E	probably damaging	Het
Zfp281	T	A	1: 136,626,940	I552N	possibly damaging	Het
Zzef1	T	A	11: 72,826,067	I361K	probably damaging	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
R4751:Tsc1	UTSW	2	28679081	missense	probably damaging	0.96
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
R7608:Tsc1	UTSW	2	28658736	missense	probably benign	0.01
R7677:Tsc1	UTSW	2	28672817	missense	probably benign	0.11
R7791:Tsc1	UTSW	2	28681948	missense	probably damaging	1.00
R8021:Tsc1	UTSW	2	28686889	missense	possibly damaging	0.67
R8203:Tsc1	UTSW	2	28672995	splice site	probably null
R8228:Tsc1	UTSW	2	28676129	missense	probably benign	0.23

Predicted Primers

PCR Primer
(F):5'- ACTGTTGGCTCACTTCCCAG -3'
(R):5'- ACTCTCTGCCCTCTGTCAGAAG -3'

Sequencing Primer
(F):5'- AGTTCCAAAAGCTTCCTGGG -3'
(R):5'- CCTCTGTCAGAAGGACCTCTG -3'

Posted On

2019-10-17