TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8889	26890;26891;26892	chr2:178713993;178713992;178713991	chr2:179578720;179578719;179578718
N2AB	8572	25939;25940;25941	chr2:178713993;178713992;178713991	chr2:179578720;179578719;179578718
N2A	7645	23158;23159;23160	chr2:178713993;178713992;178713991	chr2:179578720;179578719;179578718
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: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-74
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0749
• 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/V	rs879115210	None	0.122	D	0.269	0.406	None	gnomAD-4.0.0	3.60103E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93759E-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	0.9129	likely_pathogenic	0.9427	pathogenic	-3.025	Highly Destabilizing	0.931	D	0.705	prob.neutral	None	None	None	None	N
I/C	0.9109	likely_pathogenic	0.9433	pathogenic	-2.243	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
I/D	0.9906	likely_pathogenic	0.9939	pathogenic	-3.682	Highly Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
I/E	0.9831	likely_pathogenic	0.987	pathogenic	-3.363	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
I/F	0.2813	likely_benign	0.4538	ambiguous	-1.739	Destabilizing	0.994	D	0.707	prob.neutral	D	0.571718364	None	None	N
I/G	0.9751	likely_pathogenic	0.9828	pathogenic	-3.634	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
I/H	0.9533	likely_pathogenic	0.9733	pathogenic	-3.248	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
I/K	0.9521	likely_pathogenic	0.9596	pathogenic	-2.306	Highly Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
I/L	0.1793	likely_benign	0.2496	benign	-1.185	Destabilizing	0.689	D	0.375	neutral	D	0.546680748	None	None	N
I/M	0.1536	likely_benign	0.23	benign	-1.373	Destabilizing	0.994	D	0.693	prob.neutral	D	0.580675497	None	None	N
I/N	0.8864	likely_pathogenic	0.9105	pathogenic	-3.0	Highly Destabilizing	0.998	D	0.899	deleterious	D	0.627128069	None	None	N
I/P	0.9904	likely_pathogenic	0.993	pathogenic	-1.791	Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
I/Q	0.9618	likely_pathogenic	0.9749	pathogenic	-2.657	Highly Destabilizing	0.999	D	0.904	deleterious	None	None	None	None	N
I/R	0.9301	likely_pathogenic	0.9458	pathogenic	-2.271	Highly Destabilizing	0.999	D	0.894	deleterious	None	None	None	None	N
I/S	0.9306	likely_pathogenic	0.9514	pathogenic	-3.576	Highly Destabilizing	0.994	D	0.834	deleterious	D	0.64314743	None	None	N
I/T	0.9392	likely_pathogenic	0.9576	pathogenic	-3.098	Highly Destabilizing	0.961	D	0.713	prob.delet.	D	0.601186349	None	None	N
I/V	0.1358	likely_benign	0.1529	benign	-1.791	Destabilizing	0.122	N	0.269	neutral	D	0.551292386	None	None	N
I/W	0.9274	likely_pathogenic	0.9667	pathogenic	-2.179	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/Y	0.7777	likely_pathogenic	0.8651	pathogenic	-2.015	Highly Destabilizing	0.999	D	0.794	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.