TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6691	20296;20297;20298	chr2:178727294;178727293;178727292	chr2:179592021;179592020;179592019
N2AB	6374	19345;19346;19347	chr2:178727294;178727293;178727292	chr2:179592021;179592020;179592019
N2A	5447	16564;16565;16566	chr2:178727294;178727293;178727292	chr2:179592021;179592020;179592019
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-51
• Domain position: 25
• Structural Position: 35
• Q(SASA): 0.1138
• 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
I/T	None	None	0.954	D	0.693	0.448	0.551550886788	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	0	0
I/V	rs1429994006	None	None	N	0.199	0.155	0.32471235697	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs1429994006	None	None	N	0.199	0.155	0.32471235697	gnomAD-4.0.0	4.05997E-06	None	None	None	None	N	None	1.74715E-05	0	None	0	0	None	0	0	3.6149E-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
I/A	0.739	likely_pathogenic	0.7672	pathogenic	-2.519	Highly Destabilizing	0.017	N	0.431	neutral	None	None	None	None	N
I/C	0.9652	likely_pathogenic	0.9683	pathogenic	-1.575	Destabilizing	0.996	D	0.763	deleterious	None	None	None	None	N
I/D	0.9965	likely_pathogenic	0.9974	pathogenic	-2.722	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
I/E	0.9897	likely_pathogenic	0.9925	pathogenic	-2.434	Highly Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
I/F	0.5471	ambiguous	0.5239	ambiguous	-1.401	Destabilizing	0.677	D	0.727	prob.delet.	None	None	None	None	N
I/G	0.9725	likely_pathogenic	0.9796	pathogenic	-3.116	Highly Destabilizing	0.75	D	0.763	deleterious	None	None	None	None	N
I/H	0.9912	likely_pathogenic	0.993	pathogenic	-2.614	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
I/K	0.9843	likely_pathogenic	0.9881	pathogenic	-1.749	Destabilizing	0.936	D	0.792	deleterious	D	0.530987236	None	None	N
I/L	0.201	likely_benign	0.1738	benign	-0.758	Destabilizing	None	N	0.226	neutral	D	0.528309872	None	None	N
I/M	0.2504	likely_benign	0.2176	benign	-0.764	Destabilizing	0.487	N	0.66	neutral	N	0.512376002	None	None	N
I/N	0.9625	likely_pathogenic	0.9731	pathogenic	-2.25	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
I/P	0.9827	likely_pathogenic	0.9863	pathogenic	-1.331	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
I/Q	0.9852	likely_pathogenic	0.9881	pathogenic	-1.983	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
I/R	0.9729	likely_pathogenic	0.98	pathogenic	-1.699	Destabilizing	0.995	D	0.821	deleterious	D	0.530987236	None	None	N
I/S	0.913	likely_pathogenic	0.936	pathogenic	-2.95	Highly Destabilizing	0.979	D	0.734	prob.delet.	None	None	None	None	N
I/T	0.7165	likely_pathogenic	0.7413	pathogenic	-2.503	Highly Destabilizing	0.954	D	0.693	prob.neutral	D	0.525789642	None	None	N
I/V	0.1048	likely_benign	0.1079	benign	-1.331	Destabilizing	None	N	0.199	neutral	N	0.408471321	None	None	N
I/W	0.9883	likely_pathogenic	0.9879	pathogenic	-1.79	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
I/Y	0.9499	likely_pathogenic	0.9538	pathogenic	-1.502	Destabilizing	0.968	D	0.777	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.