TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23884	71875;71876;71877	chr2:178574482;178574481;178574480	chr2:179439209;179439208;179439207
N2AB	22243	66952;66953;66954	chr2:178574482;178574481;178574480	chr2:179439209;179439208;179439207
N2A	21316	64171;64172;64173	chr2:178574482;178574481;178574480	chr2:179439209;179439208;179439207
N2B	14819	44680;44681;44682	chr2:178574482;178574481;178574480	chr2:179439209;179439208;179439207
Novex-1	14944	45055;45056;45057	chr2:178574482;178574481;178574480	chr2:179439209;179439208;179439207
Novex-2	15011	45256;45257;45258	chr2:178574482;178574481;178574480	chr2:179439209;179439208;179439207
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-61
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.4206
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
N/K	None	None	0.977	N	0.543	0.296	0.234412748748	gnomAD-4.0.0	7.20193E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.87501E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
N/A	0.2919	likely_benign	0.3195	benign	-0.88	Destabilizing	0.983	D	0.641	neutral	None	None	None	None	I
N/C	0.2164	likely_benign	0.2079	benign	-0.059	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
N/D	0.1989	likely_benign	0.2282	benign	-0.252	Destabilizing	0.977	D	0.447	neutral	N	0.484136942	None	None	I
N/E	0.4892	ambiguous	0.561	ambiguous	-0.082	Destabilizing	0.983	D	0.516	neutral	None	None	None	None	I
N/F	0.6079	likely_pathogenic	0.6364	pathogenic	-0.632	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	I
N/G	0.357	ambiguous	0.3784	ambiguous	-1.241	Destabilizing	0.983	D	0.435	neutral	None	None	None	None	I
N/H	0.1437	likely_benign	0.1529	benign	-0.609	Destabilizing	0.235	N	0.322	neutral	N	0.499087751	None	None	I
N/I	0.2783	likely_benign	0.2806	benign	0.064	Stabilizing	0.997	D	0.727	prob.delet.	N	0.510728897	None	None	I
N/K	0.2932	likely_benign	0.3424	ambiguous	0.2	Stabilizing	0.977	D	0.543	neutral	N	0.443234469	None	None	I
N/L	0.2617	likely_benign	0.2664	benign	0.064	Stabilizing	0.995	D	0.708	prob.delet.	None	None	None	None	I
N/M	0.3568	ambiguous	0.3678	ambiguous	0.169	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
N/P	0.4745	ambiguous	0.5391	ambiguous	-0.223	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
N/Q	0.3675	ambiguous	0.414	ambiguous	-0.347	Destabilizing	0.995	D	0.63	neutral	None	None	None	None	I
N/R	0.3231	likely_benign	0.3676	ambiguous	0.146	Stabilizing	0.995	D	0.606	neutral	None	None	None	None	I
N/S	0.1115	likely_benign	0.1177	benign	-0.74	Destabilizing	0.977	D	0.414	neutral	N	0.483443508	None	None	I
N/T	0.1433	likely_benign	0.1528	benign	-0.356	Destabilizing	0.989	D	0.556	neutral	N	0.341355321	None	None	I
N/V	0.2663	likely_benign	0.2715	benign	-0.223	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	I
N/W	0.8291	likely_pathogenic	0.8454	pathogenic	-0.388	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
N/Y	0.2057	likely_benign	0.2113	benign	-0.097	Destabilizing	0.993	D	0.692	prob.neutral	N	0.48147455	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.