TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24235	72928;72929;72930	chr2:178573429;178573428;178573427	chr2:179438156;179438155;179438154
N2AB	22594	68005;68006;68007	chr2:178573429;178573428;178573427	chr2:179438156;179438155;179438154
N2A	21667	65224;65225;65226	chr2:178573429;178573428;178573427	chr2:179438156;179438155;179438154
N2B	15170	45733;45734;45735	chr2:178573429;178573428;178573427	chr2:179438156;179438155;179438154
Novex-1	15295	46108;46109;46110	chr2:178573429;178573428;178573427	chr2:179438156;179438155;179438154
Novex-2	15362	46309;46310;46311	chr2:178573429;178573428;178573427	chr2:179438156;179438155;179438154
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-64
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2828
• Predicted PPI site: N

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
T/I	rs1477680606	None	0.997	D	0.736	0.48	0.591526896791	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1477680606	None	0.997	D	0.736	0.48	0.591526896791	gnomAD-4.0.0	1.97551E-06	None	None	None	None	N	None	2.78963E-05	2.26552E-05	None	0	0	None	0	0	0	0	0
T/N	rs1477680606	None	0.235	N	0.275	0.306	0.341460817117	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	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
T/A	0.1475	likely_benign	0.1468	benign	-0.452	Destabilizing	0.977	D	0.421	neutral	D	0.523236834	None	None	N
T/C	0.5251	ambiguous	0.5311	ambiguous	-0.54	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
T/D	0.6395	likely_pathogenic	0.6941	pathogenic	-1.724	Destabilizing	0.99	D	0.67	neutral	None	None	None	None	N
T/E	0.6426	likely_pathogenic	0.6777	pathogenic	-1.693	Destabilizing	0.995	D	0.671	neutral	None	None	None	None	N
T/F	0.5835	likely_pathogenic	0.5335	ambiguous	-0.686	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
T/G	0.2277	likely_benign	0.2306	benign	-0.717	Destabilizing	0.966	D	0.597	neutral	None	None	None	None	N
T/H	0.4069	ambiguous	0.4318	ambiguous	-1.194	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
T/I	0.73	likely_pathogenic	0.6818	pathogenic	0.167	Stabilizing	0.997	D	0.736	prob.delet.	D	0.528727105	None	None	N
T/K	0.4062	ambiguous	0.429	ambiguous	-0.753	Destabilizing	0.995	D	0.677	prob.neutral	None	None	None	None	N
T/L	0.221	likely_benign	0.2113	benign	0.167	Stabilizing	0.991	D	0.604	neutral	None	None	None	None	N
T/M	0.153	likely_benign	0.1397	benign	0.559	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
T/N	0.1646	likely_benign	0.2088	benign	-1.122	Destabilizing	0.235	N	0.275	neutral	N	0.475220353	None	None	N
T/P	0.8208	likely_pathogenic	0.7984	pathogenic	-0.007	Destabilizing	0.999	D	0.723	prob.delet.	N	0.521979155	None	None	N
T/Q	0.3341	likely_benign	0.3474	ambiguous	-1.322	Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
T/R	0.3253	likely_benign	0.3487	ambiguous	-0.515	Destabilizing	0.995	D	0.738	prob.delet.	None	None	None	None	N
T/S	0.1214	likely_benign	0.1179	benign	-1.085	Destabilizing	0.955	D	0.414	neutral	N	0.463263024	None	None	N
T/V	0.5179	ambiguous	0.479	ambiguous	-0.007	Destabilizing	0.991	D	0.548	neutral	None	None	None	None	N
T/W	0.8622	likely_pathogenic	0.8384	pathogenic	-0.821	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
T/Y	0.5939	likely_pathogenic	0.5852	pathogenic	-0.442	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N

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.