Mutagenetix > Incidental Mutation

Incidental Mutation 'R1421:Tnnt3'

159817

Institutional Source

Beutler Lab

Gene Symbol

Tnnt3

Ensembl Gene

ENSMUSG00000061723

Gene Name

troponin T3, skeletal, fast

Synonyms

skeletal muscle fast-twitch TnT, fTnT

MMRRC Submission

039477-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1421 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

142052573-142069746 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 142065103 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Glycine at position 108 (E108G)

Ref Sequence

ENSEMBL: ENSMUSP00000137111 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000074187] [ENSMUST00000078497] [ENSMUST00000105941] [ENSMUST00000105942] [ENSMUST00000105943] [ENSMUST00000105944] [ENSMUST00000128294] [ENSMUST00000105950] [ENSMUST00000105947] [ENSMUST00000105957] [ENSMUST00000105946] [ENSMUST00000105952] [ENSMUST00000105949] [ENSMUST00000105958] [ENSMUST00000105945] [ENSMUST00000105948] [ENSMUST00000105955] [ENSMUST00000105953] [ENSMUST00000105954] [ENSMUST00000179658] [ENSMUST00000146804] [ENSMUST00000169299] [ENSMUST00000180152]

AlphaFold

no structure available at present

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000054910

SMART Domains

Protein: ENSMUSP00000061994
Gene: ENSMUSG00000043795

Domain	Start	End	E-Value	Type
Pfam:DUF4643	6	259	1.3e-108	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000074187
AA Change: E84G

PolyPhen 2 Score 0.906 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000073815
Gene: ENSMUSG00000061723
AA Change: E84G

Domain	Start	End	E-Value	Type
low complexity region	4	27	N/A	INTRINSIC
Pfam:Troponin	52	194	1.5e-42	PFAM
low complexity region	233	245	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000078497
AA Change: E104G

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000077587
Gene: ENSMUSG00000061723
AA Change: E104G

Domain	Start	End	E-Value	Type
coiled coil region	1	48	N/A	INTRINSIC
Pfam:Troponin	72	214	2.1e-42	PFAM
low complexity region	253	265	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105941
AA Change: E84G

PolyPhen 2 Score 0.907 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000101561
Gene: ENSMUSG00000061723
AA Change: E84G

Domain	Start	End	E-Value	Type
low complexity region	4	27	N/A	INTRINSIC
Pfam:Troponin	52	194	2.1e-42	PFAM
low complexity region	229	245	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105942
AA Change: E75G

PolyPhen 2 Score 0.907 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000101562
Gene: ENSMUSG00000061723
AA Change: E75G

Domain	Start	End	E-Value	Type
low complexity region	4	18	N/A	INTRINSIC
Pfam:Troponin	43	185	1.7e-42	PFAM
low complexity region	224	236	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105943
AA Change: E75G

PolyPhen 2 Score 0.846 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000101563
Gene: ENSMUSG00000061723
AA Change: E75G

Domain	Start	End	E-Value	Type
low complexity region	4	18	N/A	INTRINSIC
Pfam:Troponin	43	185	1.9e-42	PFAM
low complexity region	220	236	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105944
AA Change: E86G

PolyPhen 2 Score 0.906 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000101564
Gene: ENSMUSG00000061723
AA Change: E86G

Domain	Start	End	E-Value	Type
coiled coil region	1	30	N/A	INTRINSIC
Pfam:Troponin	54	196	2e-42	PFAM
low complexity region	235	247	N/A	INTRINSIC

Predicted Effect

unknown
Transcript: ENSMUST00000128294
AA Change: E81G

SMART Domains

Protein: ENSMUSP00000116223
Gene: ENSMUSG00000061723
AA Change: E81G

Domain	Start	End	E-Value	Type
low complexity region	4	24	N/A	INTRINSIC
Pfam:Troponin	49	107	3.6e-17	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105950
AA Change: E98G

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

SMART Domains

Protein: ENSMUSP00000101570
Gene: ENSMUSG00000061723
AA Change: E98G

Domain	Start	End	E-Value	Type
coiled coil region	3	42	N/A	INTRINSIC
Pfam:Troponin	66	208	1.9e-42	PFAM
internal_repeat_1	213	240	4.67e-5	PROSPERO
low complexity region	247	259	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105947
AA Change: E95G

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

SMART Domains

Protein: ENSMUSP00000101567
Gene: ENSMUSG00000061723
AA Change: E95G

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	63	205	1.9e-42	PFAM
low complexity region	240	256	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105957
AA Change: E95G

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

SMART Domains

Protein: ENSMUSP00000101577
Gene: ENSMUSG00000061723
AA Change: E95G

Domain	Start	End	E-Value	Type
low complexity region	4	36	N/A	INTRINSIC
Pfam:Troponin	63	205	1.8e-42	PFAM
low complexity region	244	256	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105946
AA Change: E90G

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

SMART Domains

Protein: ENSMUSP00000101566
Gene: ENSMUSG00000061723
AA Change: E90G

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	58	200	1.8e-42	PFAM
low complexity region	235	251	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105952
AA Change: E95G

PolyPhen 2 Score 0.947 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000101572
Gene: ENSMUSG00000061723
AA Change: E95G

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	63	205	1.8e-42	PFAM
low complexity region	244	256	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105949
AA Change: E80G

PolyPhen 2 Score 0.906 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000101569
Gene: ENSMUSG00000061723
AA Change: E80G

Domain	Start	End	E-Value	Type
low complexity region	4	23	N/A	INTRINSIC
Pfam:Troponin	48	190	1.8e-42	PFAM
low complexity region	229	241	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105958
AA Change: E108G

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

SMART Domains

Protein: ENSMUSP00000101578
Gene: ENSMUSG00000061723
AA Change: E108G

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	76	218	2.1e-42	PFAM
low complexity region	253	269	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105945
AA Change: E84G

PolyPhen 2 Score 0.906 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000101565
Gene: ENSMUSG00000061723
AA Change: E84G

Domain	Start	End	E-Value	Type
low complexity region	4	27	N/A	INTRINSIC
Pfam:Troponin	52	194	1.5e-42	PFAM
low complexity region	233	245	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105948
AA Change: E86G

PolyPhen 2 Score 0.907 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000101568
Gene: ENSMUSG00000061723
AA Change: E86G

Domain	Start	End	E-Value	Type
coiled coil region	1	30	N/A	INTRINSIC
Pfam:Troponin	54	196	2.2e-42	PFAM
low complexity region	231	247	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105955
AA Change: E91G

PolyPhen 2 Score 0.947 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000101575
Gene: ENSMUSG00000061723
AA Change: E91G

Domain	Start	End	E-Value	Type
coiled coil region	1	36	N/A	INTRINSIC
Pfam:Troponin	59	201	2.2e-42	PFAM
low complexity region	240	252	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000105953
AA Change: E98G

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000101573
Gene: ENSMUSG00000061723
AA Change: E98G

Domain	Start	End	E-Value	Type
coiled coil region	3	42	N/A	INTRINSIC
Pfam:Troponin	66	208	1.9e-42	PFAM
low complexity region	247	259	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000105954
AA Change: E99G

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000101574
Gene: ENSMUSG00000061723
AA Change: E99G

Domain	Start	End	E-Value	Type
coiled coil region	1	44	N/A	INTRINSIC
Pfam:Troponin	67	209	1.9e-42	PFAM
low complexity region	248	260	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125649

Predicted Effect

possibly damaging
Transcript: ENSMUST00000179658
AA Change: E108G

PolyPhen 2 Score 0.947 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000136278
Gene: ENSMUSG00000061723
AA Change: E108G

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	76	212	1.5e-36	PFAM
low complexity region	257	269	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000146804
AA Change: E81G

PolyPhen 2 Score 0.907 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000116087
Gene: ENSMUSG00000061723
AA Change: E81G

Domain	Start	End	E-Value	Type
low complexity region	10	24	N/A	INTRINSIC
Pfam:Troponin	49	191	1.4e-40	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000169299
AA Change: E90G

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

SMART Domains

Protein: ENSMUSP00000127854
Gene: ENSMUSG00000061723
AA Change: E90G

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	58	200	1.8e-42	PFAM
low complexity region	235	251	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000180152
AA Change: E108G

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000137111
Gene: ENSMUSG00000061723
AA Change: E108G

Domain	Start	End	E-Value	Type
coiled coil region	1	28	N/A	INTRINSIC
Pfam:Troponin	76	218	5.1e-42	PFAM
internal_repeat_1	223	250	2.76e-5	PROSPERO
low complexity region	257	269	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153262

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144259

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151580

Meta Mutation Damage Score

0.6817

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.2%
20x: 92.7%

Validation Efficiency

96% (54/56)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The binding of Ca(2+) to the trimeric troponin complex initiates the process of muscle contraction. Increased Ca(2+) concentrations produce a conformational change in the troponin complex that is transmitted to tropomyosin dimers situated along actin filaments. The altered conformation permits increased interaction between a myosin head and an actin filament which, ultimately, produces a muscle contraction. The troponin complex has protein subunits C, I, and T. Subunit C binds Ca(2+) and subunit I binds to actin and inhibits actin-myosin interaction. Subunit T binds the troponin complex to the tropomyosin complex and is also required for Ca(2+)-mediated activation of actomyosin ATPase activity. There are 3 different troponin T genes that encode tissue-specific isoforms of subunit T for fast skeletal-, slow skeletal-, and cardiac-muscle. This gene encodes fast skeletal troponin T protein; also known as troponin T type 3. Alternative splicing results in multiple transcript variants encoding additional distinct troponin T type 3 isoforms. A developmentally regulated switch between fetal/neonatal and adult troponin T type 3 isoforms occurs. Additional splice variants have been described but their biological validity has not been established. Mutations in this gene may cause distal arthrogryposis multiplex congenita type 2B (DA2B). [provided by RefSeq, Oct 2009]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit neonatal lethality, decreased fetal weight, liver and kidney hemorrhage and thin diaphragm. Mice heterozygous for this allele exhibit growth retardation with mild skeleton defects. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 50 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2ml1	T	C	6: 128,520,923 (GRCm39)	T1344A	probably benign	Het
Abcf1	G	A	17: 36,271,801 (GRCm39)	A375V	probably damaging	Het
Adam20	T	A	8: 41,249,784 (GRCm39)	H631Q	possibly damaging	Het
Adcy10	T	C	1: 165,391,516 (GRCm39)	S1258P	probably damaging	Het
Agtpbp1	A	G	13: 59,643,389 (GRCm39)	I717T	possibly damaging	Het
Ahnak	T	A	19: 8,992,995 (GRCm39)	F4760I	possibly damaging	Het
Ano6	A	G	15: 95,811,266 (GRCm39)	K122R	probably benign	Het
Arhgap5	T	C	12: 52,563,631 (GRCm39)	C201R	probably damaging	Het
Atg16l1	T	C	1: 87,714,080 (GRCm39)		probably benign	Het
Cdhr3	A	T	12: 33,110,291 (GRCm39)	I331K	probably damaging	Het
Coq8a	A	G	1: 179,998,006 (GRCm39)		probably benign	Het
Crebbp	A	G	16: 3,942,511 (GRCm39)	V662A	probably damaging	Het
Cspg4	T	A	9: 56,803,910 (GRCm39)	M1667K	probably benign	Het
Dnah7a	A	G	1: 53,580,032 (GRCm39)		probably benign	Het
Dnajc6	A	T	4: 101,468,513 (GRCm39)	Y251F	probably damaging	Het
Dpy19l4	A	T	4: 11,304,011 (GRCm39)	M133K	probably benign	Het
Emb	T	C	13: 117,408,624 (GRCm39)	Y322H	probably benign	Het
Gcm1	A	T	9: 77,966,982 (GRCm39)	H67L	probably damaging	Het
Gls2	A	T	10: 128,037,217 (GRCm39)	K253*	probably null	Het
Gm28042	T	A	2: 119,866,944 (GRCm39)	S196T	probably benign	Het
Gm43302	T	C	5: 105,365,215 (GRCm39)	T598A	probably benign	Het
Gramd1a	T	A	7: 30,842,291 (GRCm39)	Q90L	probably damaging	Het
Grhl2	A	G	15: 37,309,960 (GRCm39)	Y352C	probably damaging	Het
Ifi203-ps	T	C	1: 173,625,563 (GRCm39)		noncoding transcript	Het
Ifitm2	T	C	7: 140,534,972 (GRCm39)	I121V	probably benign	Het
Insyn2a	A	T	7: 134,500,960 (GRCm39)		probably benign	Het
Kptn	T	G	7: 15,856,949 (GRCm39)		probably benign	Het
L2hgdh	C	T	12: 69,748,092 (GRCm39)	D345N	probably benign	Het
Lgals12	T	C	19: 7,584,079 (GRCm39)	H6R	probably benign	Het
Lrrc4b	A	G	7: 44,110,475 (GRCm39)	I116V	probably benign	Het
Misp	A	G	10: 79,662,681 (GRCm39)	D366G	probably damaging	Het
Nav1	T	C	1: 135,512,748 (GRCm39)	E104G	probably damaging	Het
Nup155	A	T	15: 8,187,244 (GRCm39)	H1391L	probably damaging	Het
Parp1	T	C	1: 180,427,653 (GRCm39)		probably benign	Het
Pikfyve	G	A	1: 65,310,470 (GRCm39)	G1919D	probably damaging	Het
Pomt1	A	G	2: 32,126,765 (GRCm39)		probably benign	Het
Prrc2b	C	T	2: 32,090,990 (GRCm39)	S454F	possibly damaging	Het
Selenbp1	T	C	3: 94,851,183 (GRCm39)	S360P	probably benign	Het
Slc6a12	T	A	6: 121,336,085 (GRCm39)	I352N	probably damaging	Het
Snx9	G	A	17: 5,952,759 (GRCm39)	G197D	probably benign	Het
Ston1	T	C	17: 88,943,221 (GRCm39)	V209A	probably benign	Het
Taf7l2	A	G	10: 115,949,343 (GRCm39)	V61A	probably damaging	Het
Tex36	A	T	7: 133,197,078 (GRCm39)		probably null	Het
Vmn2r98	T	A	17: 19,285,440 (GRCm39)	F87I	probably damaging	Het
Vwa8	C	T	14: 79,145,670 (GRCm39)	R116C	probably damaging	Het
Wdr64	T	C	1: 175,594,716 (GRCm39)	I479T	possibly damaging	Het
Xrcc5	A	G	1: 72,349,636 (GRCm39)	N22D	probably benign	Het
Zfp407	C	T	18: 84,577,898 (GRCm39)	A1072T	probably benign	Het
Zfp735	C	A	11: 73,601,523 (GRCm39)	L156I	probably benign	Het
Zfp820	A	T	17: 22,038,861 (GRCm39)	Y156N	possibly damaging	Het

Other mutations in Tnnt3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02247:Tnnt3	APN	7	142,062,062 (GRCm39)	intron	probably benign
IGL02376:Tnnt3	APN	7	142,066,295 (GRCm39)	missense	possibly damaging	0.64
R0432:Tnnt3	UTSW	7	142,065,823 (GRCm39)	missense	probably benign	0.09
R0463:Tnnt3	UTSW	7	142,066,072 (GRCm39)	missense	probably benign	0.25
R1521:Tnnt3	UTSW	7	142,069,562 (GRCm39)	nonsense	probably null
R1789:Tnnt3	UTSW	7	142,066,101 (GRCm39)	missense	probably damaging	1.00
R1990:Tnnt3	UTSW	7	142,065,262 (GRCm39)	missense	possibly damaging	0.78
R1991:Tnnt3	UTSW	7	142,065,262 (GRCm39)	missense	possibly damaging	0.78
R2029:Tnnt3	UTSW	7	142,066,364 (GRCm39)	splice site	probably benign
R2216:Tnnt3	UTSW	7	142,066,301 (GRCm39)	missense	probably benign	0.03
R4779:Tnnt3	UTSW	7	142,068,020 (GRCm39)	intron	probably benign
R5568:Tnnt3	UTSW	7	142,065,777 (GRCm39)	missense	probably damaging	0.98
R5756:Tnnt3	UTSW	7	142,056,495 (GRCm39)	critical splice donor site	probably null
R5994:Tnnt3	UTSW	7	142,065,003 (GRCm39)	missense	probably damaging	1.00
R6265:Tnnt3	UTSW	7	142,055,382 (GRCm39)	missense	probably damaging	0.98
R7658:Tnnt3	UTSW	7	142,065,833 (GRCm39)	nonsense	probably null
R8280:Tnnt3	UTSW	7	142,055,359 (GRCm39)	missense	unknown
R9074:Tnnt3	UTSW	7	142,065,823 (GRCm39)	missense	probably benign	0.05

Predicted Primers

PCR Primer
(F):5'- CTGAGCCAGGTCACCTCAAGAATG -3'
(R):5'- AACAGGAAGGCACAGTCCTTACCG -3'

Sequencing Primer
(F):5'- ACCTCAAGAATGGTACTGGCTTC -3'
(R):5'- ACCGCCAATCTGTTCTGG -3'

Posted On

2014-03-14