TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32392	97399;97400;97401	chr2:178542680;178542679;178542678	chr2:179407407;179407406;179407405
N2AB	30751	92476;92477;92478	chr2:178542680;178542679;178542678	chr2:179407407;179407406;179407405
N2A	29824	89695;89696;89697	chr2:178542680;178542679;178542678	chr2:179407407;179407406;179407405
N2B	23327	70204;70205;70206	chr2:178542680;178542679;178542678	chr2:179407407;179407406;179407405
Novex-1	23452	70579;70580;70581	chr2:178542680;178542679;178542678	chr2:179407407;179407406;179407405
Novex-2	23519	70780;70781;70782	chr2:178542680;178542679;178542678	chr2:179407407;179407406;179407405
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-154
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.154
• 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/S	None	None	0.942	N	0.779	0.638	0.809007091605	gnomAD-4.0.0	2.05352E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.97199E-05
I/T	None	None	0.822	N	0.758	0.46	0.709166840936	gnomAD-4.0.0	6.84507E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.999E-07	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	0.9019	likely_pathogenic	0.8336	pathogenic	-2.676	Highly Destabilizing	0.754	D	0.667	neutral	None	None	None	None	N
I/C	0.9005	likely_pathogenic	0.8697	pathogenic	-2.129	Highly Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
I/D	0.9985	likely_pathogenic	0.9969	pathogenic	-3.261	Highly Destabilizing	0.993	D	0.832	deleterious	None	None	None	None	N
I/E	0.9937	likely_pathogenic	0.9872	pathogenic	-2.986	Highly Destabilizing	0.978	D	0.831	deleterious	None	None	None	None	N
I/F	0.3448	ambiguous	0.2612	benign	-1.594	Destabilizing	0.942	D	0.677	prob.neutral	D	0.524901421	None	None	N
I/G	0.9857	likely_pathogenic	0.9735	pathogenic	-3.282	Highly Destabilizing	0.978	D	0.822	deleterious	None	None	None	None	N
I/H	0.9838	likely_pathogenic	0.9686	pathogenic	-2.873	Highly Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
I/K	0.9843	likely_pathogenic	0.9708	pathogenic	-2.266	Highly Destabilizing	0.956	D	0.821	deleterious	None	None	None	None	N
I/L	0.1682	likely_benign	0.1321	benign	-0.9	Destabilizing	0.125	N	0.426	neutral	N	0.473643094	None	None	N
I/M	0.2129	likely_benign	0.1591	benign	-0.922	Destabilizing	0.489	N	0.451	neutral	N	0.501812483	None	None	N
I/N	0.9766	likely_pathogenic	0.9604	pathogenic	-2.772	Highly Destabilizing	0.97	D	0.835	deleterious	N	0.513675767	None	None	N
I/P	0.9953	likely_pathogenic	0.9912	pathogenic	-1.476	Destabilizing	0.993	D	0.839	deleterious	None	None	None	None	N
I/Q	0.9807	likely_pathogenic	0.9657	pathogenic	-2.534	Highly Destabilizing	0.978	D	0.835	deleterious	None	None	None	None	N
I/R	0.9717	likely_pathogenic	0.9463	pathogenic	-2.081	Highly Destabilizing	0.956	D	0.828	deleterious	None	None	None	None	N
I/S	0.963	likely_pathogenic	0.9373	pathogenic	-3.454	Highly Destabilizing	0.942	D	0.779	deleterious	N	0.512661809	None	None	N
I/T	0.9382	likely_pathogenic	0.8951	pathogenic	-3.014	Highly Destabilizing	0.822	D	0.758	deleterious	N	0.489442219	None	None	N
I/V	0.1044	likely_benign	0.0926	benign	-1.476	Destabilizing	0.006	N	0.194	neutral	N	0.477048759	None	None	N
I/W	0.9535	likely_pathogenic	0.9276	pathogenic	-2.062	Highly Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
I/Y	0.8888	likely_pathogenic	0.8385	pathogenic	-1.768	Destabilizing	0.978	D	0.787	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.