TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34402	103429;103430;103431	chr2:178533411;178533410;178533409	chr2:179398138;179398137;179398136
N2AB	32761	98506;98507;98508	chr2:178533411;178533410;178533409	chr2:179398138;179398137;179398136
N2A	31834	95725;95726;95727	chr2:178533411;178533410;178533409	chr2:179398138;179398137;179398136
N2B	25337	76234;76235;76236	chr2:178533411;178533410;178533409	chr2:179398138;179398137;179398136
Novex-1	25462	76609;76610;76611	chr2:178533411;178533410;178533409	chr2:179398138;179398137;179398136
Novex-2	25529	76810;76811;76812	chr2:178533411;178533410;178533409	chr2:179398138;179398137;179398136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-162
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.6247
• 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
P/S	rs1361480669	None	0.58	N	0.299	0.29	0.329540904979	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
P/A	0.0929	likely_benign	0.0832	benign	-0.485	Destabilizing	0.046	N	0.321	neutral	N	0.506334303	None	None	N
P/C	0.6136	likely_pathogenic	0.5893	pathogenic	-0.622	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
P/D	0.5109	ambiguous	0.4758	ambiguous	-0.277	Destabilizing	0.986	D	0.625	neutral	None	None	None	None	N
P/E	0.2891	likely_benign	0.2629	benign	-0.398	Destabilizing	0.986	D	0.613	neutral	None	None	None	None	N
P/F	0.5435	ambiguous	0.5266	ambiguous	-0.737	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
P/G	0.5003	ambiguous	0.4789	ambiguous	-0.609	Destabilizing	0.91	D	0.536	neutral	None	None	None	None	N
P/H	0.244	likely_benign	0.2358	benign	-0.179	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
P/I	0.2824	likely_benign	0.2545	benign	-0.311	Destabilizing	0.986	D	0.778	deleterious	None	None	None	None	N
P/K	0.3593	ambiguous	0.3552	ambiguous	-0.405	Destabilizing	0.986	D	0.61	neutral	None	None	None	None	N
P/L	0.1172	likely_benign	0.1116	benign	-0.311	Destabilizing	0.982	D	0.685	prob.neutral	N	0.473723239	None	None	N
P/M	0.3244	likely_benign	0.2932	benign	-0.337	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
P/N	0.4238	ambiguous	0.4015	ambiguous	-0.144	Destabilizing	0.986	D	0.747	deleterious	None	None	None	None	N
P/Q	0.1834	likely_benign	0.1699	benign	-0.41	Destabilizing	0.991	D	0.689	prob.neutral	N	0.502659279	None	None	N
P/R	0.2454	likely_benign	0.2499	benign	0.129	Stabilizing	0.991	D	0.738	prob.delet.	N	0.514223067	None	None	N
P/S	0.1709	likely_benign	0.1582	benign	-0.506	Destabilizing	0.58	D	0.299	neutral	N	0.492693002	None	None	N
P/T	0.1267	likely_benign	0.1154	benign	-0.528	Destabilizing	0.939	D	0.575	neutral	N	0.504160789	None	None	N
P/V	0.2072	likely_benign	0.1869	benign	-0.334	Destabilizing	0.973	D	0.622	neutral	None	None	None	None	N
P/W	0.7536	likely_pathogenic	0.7546	pathogenic	-0.803	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
P/Y	0.5075	ambiguous	0.4925	ambiguous	-0.5	Destabilizing	0.999	D	0.751	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.