Mutagenetix > Incidental Mutation

Incidental Mutation 'R5994:Tnnt3'

481004

Institutional Source

Beutler Lab

Gene Symbol

Tnnt3

Ensembl Gene

ENSMUSG00000061723

Gene Name

troponin T3, skeletal, fast

Synonyms

fTnT, skeletal muscle fast-twitch TnT

MMRRC Submission

044173-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5994 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

142498836-142516009 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 142511266 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Glutamic Acid at position 48 (K48E)

Ref Sequence

ENSEMBL: ENSMUSP00000116087 (fasta)

Gene Model

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

probably damaging
Transcript: ENSMUST00000074187
AA Change: K51E

PolyPhen 2 Score 0.977 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000073815
Gene: ENSMUSG00000061723
AA Change: K51E

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: K71E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000077587
Gene: ENSMUSG00000061723
AA Change: K71E

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

probably damaging
Transcript: ENSMUST00000105941
AA Change: K51E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101561
Gene: ENSMUSG00000061723
AA Change: K51E

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

probably damaging
Transcript: ENSMUST00000105942
AA Change: K42E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101562
Gene: ENSMUSG00000061723
AA Change: K42E

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

probably damaging
Transcript: ENSMUST00000105943
AA Change: K42E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101563
Gene: ENSMUSG00000061723
AA Change: K42E

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

probably damaging
Transcript: ENSMUST00000105944
AA Change: K53E

PolyPhen 2 Score 0.977 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000101564
Gene: ENSMUSG00000061723
AA Change: K53E

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

probably damaging
Transcript: ENSMUST00000105945
AA Change: K51E

PolyPhen 2 Score 0.977 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000101565
Gene: ENSMUSG00000061723
AA Change: K51E

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: ENSMUST00000105946
AA Change: K57E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101566
Gene: ENSMUSG00000061723
AA Change: K57E

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: ENSMUST00000105947
AA Change: K62E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101567
Gene: ENSMUSG00000061723
AA Change: K62E

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

probably damaging
Transcript: ENSMUST00000105948
AA Change: K53E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101568
Gene: ENSMUSG00000061723
AA Change: K53E

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

probably damaging
Transcript: ENSMUST00000105949
AA Change: K47E

PolyPhen 2 Score 0.977 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000101569
Gene: ENSMUSG00000061723
AA Change: K47E

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

probably damaging
Transcript: ENSMUST00000105950
AA Change: K65E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101570
Gene: ENSMUSG00000061723
AA Change: K65E

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

probably damaging
Transcript: ENSMUST00000105952
AA Change: K62E

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000101572
Gene: ENSMUSG00000061723
AA Change: K62E

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

probably damaging
Transcript: ENSMUST00000105953
AA Change: K65E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101573
Gene: ENSMUSG00000061723
AA Change: K65E

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: K66E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101574
Gene: ENSMUSG00000061723
AA Change: K66E

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

probably damaging
Transcript: ENSMUST00000105955
AA Change: K58E

PolyPhen 2 Score 0.977 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000101575
Gene: ENSMUSG00000061723
AA Change: K58E

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: ENSMUST00000105957
AA Change: K62E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101577
Gene: ENSMUSG00000061723
AA Change: K62E

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

probably damaging
Transcript: ENSMUST00000105958
AA Change: K75E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000101578
Gene: ENSMUSG00000061723
AA Change: K75E

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

unknown
Transcript: ENSMUST00000128294
AA Change: K48E

SMART Domains

Protein: ENSMUSP00000116223
Gene: ENSMUSG00000061723
AA Change: K48E

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000146804
AA Change: K48E

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

SMART Domains

Protein: ENSMUSP00000116087
Gene: ENSMUSG00000061723
AA Change: K48E

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000169299
AA Change: K57E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000127854
Gene: ENSMUSG00000061723
AA Change: K57E

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: ENSMUST00000179658
AA Change: K75E

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000136278
Gene: ENSMUSG00000061723
AA Change: K75E

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

probably damaging
Transcript: ENSMUST00000180152
AA Change: K75E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000137111
Gene: ENSMUSG00000061723
AA Change: K75E

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: ENSMUST00000151580

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125649

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153262

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144259

Coding Region Coverage

1x: 99.9%
3x: 99.5%
10x: 97.4%
20x: 91.7%

Validation Efficiency

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: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2m	A	T	6: 121,670,903	H1118L	probably benign	Het
Abca8b	A	G	11: 109,949,766		probably null	Het
Abcb5	A	T	12: 118,965,260		probably null	Het
Adcy6	A	T	15: 98,593,664	I1016N	probably damaging	Het
Afg3l2	A	T	18: 67,429,070	C312S	probably damaging	Het
Ano8	C	T	8: 71,484,834	V89M	probably damaging	Het
Arhgap21	C	T	2: 20,881,376	G330D	possibly damaging	Het
Caskin1	T	C	17: 24,496,961	L195P	probably damaging	Het
Cfap54	A	G	10: 93,039,081	I514T	probably damaging	Het
Ctdsp2	G	A	10: 126,995,820		probably benign	Het
Cyp4x1	T	C	4: 115,121,945	I152V	probably benign	Het
Dglucy	G	A	12: 100,842,700	R219Q	probably benign	Het
Disp3	G	T	4: 148,254,284	A810E	possibly damaging	Het
Dtx4	T	C	19: 12,501,153	Y22C	probably damaging	Het
Edaradd	A	T	13: 12,478,496	I105N	probably damaging	Het
Eepd1	C	T	9: 25,603,453	P519S	probably damaging	Het
Fscn3	A	T	6: 28,430,295	S155C	probably benign	Het
Gm10134	A	T	2: 28,506,246	E51V	probably damaging	Het
Gm7247	C	T	14: 51,364,348	S26F	probably benign	Het
Golga7	T	C	8: 23,250,265	E83G	probably benign	Het
Gpr12	T	C	5: 146,583,431	H227R	probably damaging	Het
Hoxa2	T	G	6: 52,164,392	S85R	possibly damaging	Het
Hrnr	T	C	3: 93,332,300	S3282P	unknown	Het
Ift74	C	A	4: 94,691,724	T543K	possibly damaging	Het
Klf10	C	A	15: 38,296,041	R420L	probably damaging	Het
Krt77	T	A	15: 101,862,855	I338F	probably damaging	Het
Limch1	A	T	5: 66,974,622	S152C	probably damaging	Het
Mgat4e	T	A	1: 134,541,496	H270L	probably benign	Het
Myrf	A	T	19: 10,219,117	L504Q	probably null	Het
Nckipsd	A	G	9: 108,813,977	Q366R	probably benign	Het
Npy5r	A	T	8: 66,682,099	V14D	probably benign	Het
Nrap	T	A	19: 56,351,599	R830*	probably null	Het
Ogfrl1	A	T	1: 23,378,989	Y103N	probably damaging	Het
Olfr978	A	T	9: 39,994,223	R138*	probably null	Het
P2rx4	T	A	5: 122,725,079	L232H	probably damaging	Het
Pabpc2	A	T	18: 39,773,894	T71S	probably benign	Het
Paip2b	C	A	6: 83,808,885	S121I	probably damaging	Het
Pofut1	C	T	2: 153,261,229	T261I	possibly damaging	Het
Ppp6c	G	T	2: 39,210,992	T46K	possibly damaging	Het
Prkd2	C	A	7: 16,850,336	H371Q	probably benign	Het
Prrc2c	A	T	1: 162,674,156		probably null	Het
Psd3	C	T	8: 67,719,968	A894T	probably damaging	Het
Pygm	A	T	19: 6,398,043		probably null	Het
Pzp	A	T	6: 128,491,597	M989K	probably damaging	Het
Ralgapa2	A	T	2: 146,361,453	S1159T	probably benign	Het
Rapgefl1	T	C	11: 98,850,160	F575L	probably benign	Het
Rassf6	A	G	5: 90,617,768	L28S	probably damaging	Het
Rbp3	G	T	14: 33,954,900	K268N	probably damaging	Het
Rela	C	T	19: 5,647,064	T433M	possibly damaging	Het
Rnf103	T	A	6: 71,496,910	S102R	probably damaging	Het
Scarf2	A	G	16: 17,806,379	N516S	probably damaging	Het
Sdcbp2	T	C	2: 151,587,483	I241T	probably damaging	Het
Sept7	T	C	9: 25,288,198	I131T	possibly damaging	Het
Sh3pxd2b	T	C	11: 32,407,570	F191L	probably damaging	Het
Siglec15	C	A	18: 78,047,375	C236F	probably damaging	Het
Slc11a2	T	C	15: 100,397,681	T520A	probably benign	Het
Slc26a11	C	A	11: 119,379,912	F553L	probably benign	Het
Smchd1	G	A	17: 71,365,409	P1596S	possibly damaging	Het
Taar7b	A	G	10: 24,000,348	H137R	probably damaging	Het
Thap12	T	A	7: 98,716,030	C468*	probably null	Het
Timp4	C	T	6: 115,247,354	G118D	probably damaging	Het
Trmt10a	T	A	3: 138,156,714	I255N	probably damaging	Het
Ttll10	T	C	4: 156,048,732		probably null	Het
Ube4b	A	G	4: 149,372,932	Y283H	probably damaging	Het
Ucp1	G	T	8: 83,293,938	V126L	possibly damaging	Het
Unc13b	T	A	4: 43,172,596		probably benign	Het
Vps13b	T	C	15: 35,875,772	S2768P	probably damaging	Het
Zcchc6	T	G	13: 59,789,209	Y806S	probably damaging	Het
Zfp101	T	A	17: 33,380,962	M607L	probably benign	Het
Zfp292	C	T	4: 34,805,464	V2527M	possibly damaging	Het
Zfp503	T	A	14: 21,985,562	T429S	possibly damaging	Het

Other mutations in Tnnt3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02247:Tnnt3	APN	7	142508325	intron	probably benign
IGL02376:Tnnt3	APN	7	142512558	missense	possibly damaging	0.64
R0432:Tnnt3	UTSW	7	142512086	missense	probably benign	0.09
R0463:Tnnt3	UTSW	7	142512335	missense	probably benign	0.25
R1421:Tnnt3	UTSW	7	142511366	missense	probably damaging	0.97
R1521:Tnnt3	UTSW	7	142515825	nonsense	probably null
R1789:Tnnt3	UTSW	7	142512364	missense	probably damaging	1.00
R1990:Tnnt3	UTSW	7	142511525	missense	possibly damaging	0.78
R1991:Tnnt3	UTSW	7	142511525	missense	possibly damaging	0.78
R2029:Tnnt3	UTSW	7	142512627	splice site	probably benign
R2216:Tnnt3	UTSW	7	142512564	missense	probably benign	0.03
R4779:Tnnt3	UTSW	7	142514283	intron	probably benign
R5568:Tnnt3	UTSW	7	142512040	missense	probably damaging	0.98
R5756:Tnnt3	UTSW	7	142502758	critical splice donor site	probably null
R6265:Tnnt3	UTSW	7	142501645	missense	probably damaging	0.98
R7658:Tnnt3	UTSW	7	142512096	nonsense	probably null
R8280:Tnnt3	UTSW	7	142501622	missense	unknown
R9074:Tnnt3	UTSW	7	142512086	missense	probably benign	0.05

Predicted Primers

PCR Primer
(F):5'- TTCATGATCAGCCAGGGCCTAG -3'
(R):5'- GCGAATTCTTTGCTGCTCAG -3'

Sequencing Primer
(F):5'- GCCTAGGTTCCTCCGTGAC -3'
(R):5'- TTCTCCTGCAGCCAAGAGG -3'

Posted On

2017-06-26