Mutagenetix > Incidental Mutation

Incidental Mutation 'R5245:Tnnt1'

470630

Institutional Source

Beutler Lab

Gene Symbol

Tnnt1

Ensembl Gene

ENSMUSG00000064179

Gene Name

troponin T1, skeletal, slow

Synonyms

Tnt, ssTnT, sTnT, skeletal muscle slow-twitch TnT

MMRRC Submission

042816-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.304) question?

Stock #

R5245 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

4507568-4518974 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 4513066 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 72 (D72G)

Ref Sequence

ENSEMBL: ENSMUSP00000129409 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000071798] [ENSMUST00000108587] [ENSMUST00000163538] [ENSMUST00000163560] [ENSMUST00000163710] [ENSMUST00000163722] [ENSMUST00000166161] [ENSMUST00000166268] [ENSMUST00000166959] [ENSMUST00000178163]

AlphaFold

O88346

Predicted Effect

probably damaging
Transcript: ENSMUST00000071798
AA Change: D64G

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

SMART Domains

Protein: ENSMUSP00000071704
Gene: ENSMUSG00000064179
AA Change: D64G

Domain	Start	End	E-Value	Type
low complexity region	5	56	N/A	INTRINSIC
Pfam:Troponin	68	210	7.3e-40	PFAM
low complexity region	246	259	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000086502

Predicted Effect

probably damaging
Transcript: ENSMUST00000108587
AA Change: D65G

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000104228
Gene: ENSMUSG00000064179
AA Change: D65G

Domain	Start	End	E-Value	Type
low complexity region	5	57	N/A	INTRINSIC
Pfam:Troponin	69	205	3e-36	PFAM
Pfam:Troponin	197	260	4.8e-8	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000163538
AA Change: D64G

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

SMART Domains

Protein: ENSMUSP00000127964
Gene: ENSMUSG00000064179
AA Change: D64G

Domain	Start	End	E-Value	Type
low complexity region	5	56	N/A	INTRINSIC
Pfam:Troponin	68	160	4.4e-26	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000163560

Predicted Effect

probably damaging
Transcript: ENSMUST00000163710
AA Change: D53G

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000129626
Gene: ENSMUSG00000064179
AA Change: D53G

Domain	Start	End	E-Value	Type
coiled coil region	2	29	N/A	INTRINSIC
Pfam:Troponin	57	199	1.9e-39	PFAM
low complexity region	235	248	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000163722
AA Change: D72G

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

SMART Domains

Protein: ENSMUSP00000129409
Gene: ENSMUSG00000064179
AA Change: D72G

Domain	Start	End	E-Value	Type
low complexity region	17	64	N/A	INTRINSIC
Pfam:Troponin	76	118	1.9e-13	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000166161
AA Change: D52G

PolyPhen 2 Score 0.985 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000125795
Gene: ENSMUSG00000064179
AA Change: D52G

Domain	Start	End	E-Value	Type
low complexity region	5	46	N/A	INTRINSIC
Pfam:Troponin	56	198	3.4e-40	PFAM
low complexity region	234	247	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000166268
AA Change: D54G

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000128476
Gene: ENSMUSG00000064179
AA Change: D54G

Domain	Start	End	E-Value	Type
coiled coil region	2	28	N/A	INTRINSIC
Pfam:Troponin	58	200	1.6e-38	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000166959
AA Change: D65G

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000129109
Gene: ENSMUSG00000064179
AA Change: D65G

Domain	Start	End	E-Value	Type
low complexity region	5	57	N/A	INTRINSIC
Pfam:Troponin	69	192	1.5e-31	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000178163
AA Change: D64G

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000137198
Gene: ENSMUSG00000064179
AA Change: D64G

Domain	Start	End	E-Value	Type
low complexity region	5	40	N/A	INTRINSIC
low complexity region	44	55	N/A	INTRINSIC
Pfam:Troponin	68	210	7.3e-40	PFAM
low complexity region	246	259	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000169571

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000168111

Meta Mutation Damage Score

0.8664

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.2%
20x: 95.3%

Validation Efficiency

100% (51/51)

MGI Phenotype

FUNCTION: This gene encodes the slow skeletal tropomyosin-binding subunit of the troponin complex and plays an essential role in the regulation of striated muscle contraction. In humans, mutations in this gene are associated with nemaline myopathy type 5. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2013]
PHENOTYPE: Mice homozygous for a null or hypomorphic allele show small and loss of type I slow skeletal muscle fibers with compensatory hypertrophy of type II fast fibers and reduced contractile force and tolerance of skeletal muscle fibers. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 45 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abhd17b	T	A	19: 21,661,624 (GRCm39)	Y270*	probably null	Het
Akap9	A	T	5: 4,026,209 (GRCm39)	Q59L	probably damaging	Het
Aloxe3	A	T	11: 69,020,502 (GRCm39)	Q182L	probably benign	Het
Arhgef5	G	T	6: 43,242,614 (GRCm39)		probably benign	Het
Bcas3	T	A	11: 85,449,912 (GRCm39)	N663K	probably damaging	Het
Cimap3	T	C	3: 105,921,770 (GRCm39)	H51R	possibly damaging	Het
Cntfr	A	T	4: 41,670,879 (GRCm39)	W95R	possibly damaging	Het
Dcun1d4	A	G	5: 73,714,657 (GRCm39)	T275A	probably benign	Het
Eps8l1	A	G	7: 4,473,873 (GRCm39)	R227G	probably damaging	Het
Ets2	G	A	16: 95,513,304 (GRCm39)	W160*	probably null	Het
Flt4	AC	ACC	11: 49,541,861 (GRCm39)		probably null	Het
Fsip2	A	G	2: 82,823,505 (GRCm39)	M6413V	probably benign	Het
Gm14401	C	T	2: 176,778,471 (GRCm39)	P186S	probably damaging	Het
Hrc	G	A	7: 44,984,855 (GRCm39)	G2D	probably damaging	Het
Kcnq3	A	G	15: 65,903,284 (GRCm39)	V142A	possibly damaging	Het
Lama3	G	A	18: 12,552,950 (GRCm39)	C454Y	probably damaging	Het
Lrrk2	A	G	15: 91,680,292 (GRCm39)	T2068A	probably damaging	Het
Mab21l2	T	C	3: 86,454,799 (GRCm39)	E67G	possibly damaging	Het
Map3k5	G	A	10: 20,016,437 (GRCm39)	V1343I	probably benign	Het
Mcm4	T	A	16: 15,448,289 (GRCm39)	T423S	probably benign	Het
Mmp16	A	G	4: 18,054,596 (GRCm39)		probably benign	Het
Nat3	C	T	8: 68,000,832 (GRCm39)	T237I	probably benign	Het
Nol4	A	T	18: 22,828,179 (GRCm39)	*484R	probably null	Het
Nsmf	A	G	2: 24,946,119 (GRCm39)	E202G	probably damaging	Het
Olfml2b	T	C	1: 170,496,443 (GRCm39)	V358A	probably benign	Het
Or2v2	T	A	11: 49,004,116 (GRCm39)	I146F	probably benign	Het
Or4b1d	T	A	2: 89,968,606 (GRCm39)	K292N	probably damaging	Het
Osbpl1a	T	C	18: 12,891,910 (GRCm39)	E466G	probably damaging	Het
Pim3	A	G	15: 88,747,404 (GRCm39)	E90G	possibly damaging	Het
Recql5	T	C	11: 115,784,385 (GRCm39)	E905G	probably damaging	Het
Rnf31	T	G	14: 55,839,163 (GRCm39)	L925R	probably damaging	Het
Secisbp2l	A	G	2: 125,589,511 (GRCm39)	V679A	probably damaging	Het
Setdb2	T	A	14: 59,663,943 (GRCm39)	E68V	probably null	Het
Shtn1	T	A	19: 59,020,652 (GRCm39)	N190I	possibly damaging	Het
Slc25a25	G	A	2: 32,311,340 (GRCm39)	Q14*	probably null	Het
Snrnp27	A	G	6: 86,659,941 (GRCm39)	S18P	unknown	Het
Srsf11	C	T	3: 157,728,981 (GRCm39)		probably benign	Het
Tbx5	T	C	5: 120,021,230 (GRCm39)	V412A	possibly damaging	Het
Tcea3	A	G	4: 135,991,813 (GRCm39)	T166A	probably benign	Het
Tdrp	A	T	8: 14,024,479 (GRCm39)		probably benign	Het
Tent5a	G	T	9: 85,208,401 (GRCm39)	Q160K	possibly damaging	Het
Tmem132e	T	C	11: 82,333,464 (GRCm39)	V624A	probably damaging	Het
Trim80	C	A	11: 115,332,398 (GRCm39)	H197N	probably damaging	Het
Zfp322a	A	T	13: 23,541,156 (GRCm39)	C195*	probably null	Het
Zfp335	A	G	2: 164,736,678 (GRCm39)	S986P	probably benign	Het

Other mutations in Tnnt1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00585:Tnnt1	APN	7	4,510,549 (GRCm39)	missense	possibly damaging	0.96
IGL01391:Tnnt1	APN	7	4,517,211 (GRCm39)	critical splice donor site	probably null
IGL01582:Tnnt1	APN	7	4,512,982 (GRCm39)	missense	probably damaging	1.00
R0098:Tnnt1	UTSW	7	4,512,044 (GRCm39)	missense	probably damaging	0.99
R0963:Tnnt1	UTSW	7	4,510,594 (GRCm39)	missense	probably damaging	1.00
R1489:Tnnt1	UTSW	7	4,510,524 (GRCm39)	nonsense	probably null
R2340:Tnnt1	UTSW	7	4,516,615 (GRCm39)	splice site	probably benign
R4224:Tnnt1	UTSW	7	4,513,006 (GRCm39)	missense	probably damaging	1.00
R4624:Tnnt1	UTSW	7	4,515,267 (GRCm39)	intron	probably benign
R4969:Tnnt1	UTSW	7	4,510,573 (GRCm39)	missense	probably damaging	1.00
R5822:Tnnt1	UTSW	7	4,519,345 (GRCm39)	nonsense	probably null
R6520:Tnnt1	UTSW	7	4,512,060 (GRCm39)	nonsense	probably null
R6556:Tnnt1	UTSW	7	4,512,576 (GRCm39)	missense	probably damaging	1.00
R6573:Tnnt1	UTSW	7	4,517,333 (GRCm39)	splice site	probably null
R6838:Tnnt1	UTSW	7	4,510,406 (GRCm39)	missense	possibly damaging	0.94
R7318:Tnnt1	UTSW	7	4,513,547 (GRCm39)	splice site	probably null
R7889:Tnnt1	UTSW	7	4,511,582 (GRCm39)	missense	probably damaging	1.00
R8405:Tnnt1	UTSW	7	4,510,592 (GRCm39)	missense	probably damaging	0.98
R9217:Tnnt1	UTSW	7	4,513,381 (GRCm39)	missense	probably benign	0.18
R9621:Tnnt1	UTSW	7	4,511,501 (GRCm39)	missense	probably benign	0.08
X0010:Tnnt1	UTSW	7	4,512,970 (GRCm39)	missense	probably damaging	0.99

Predicted Primers

PCR Primer
(F):5'- ATGGATACTGGAGTGGACCC -3'
(R):5'- TTCCTTCATGAAAACCCTGGG -3'

Sequencing Primer
(F):5'- TGTTTCTCCCAGAGACCCCAAAG -3'
(R):5'- ACATCTGCTGGAAGCCAT -3'

Posted On

2017-03-31