TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30163	90712;90713;90714	chr2:178552413;178552412;178552411	chr2:179417140;179417139;179417138
N2AB	28522	85789;85790;85791	chr2:178552413;178552412;178552411	chr2:179417140;179417139;179417138
N2A	27595	83008;83009;83010	chr2:178552413;178552412;178552411	chr2:179417140;179417139;179417138
N2B	21098	63517;63518;63519	chr2:178552413;178552412;178552411	chr2:179417140;179417139;179417138
Novex-1	21223	63892;63893;63894	chr2:178552413;178552412;178552411	chr2:179417140;179417139;179417138
Novex-2	21290	64093;64094;64095	chr2:178552413;178552412;178552411	chr2:179417140;179417139;179417138
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-148
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1285
• 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	rs1445875669	None	0.046	N	0.234	0.057	0.40722173914	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4281	ambiguous	0.3753	ambiguous	-2.273	Highly Destabilizing	0.919	D	0.724	prob.delet.	None	None	None	None	N
I/C	0.6279	likely_pathogenic	0.6122	pathogenic	-1.538	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
I/D	0.9351	likely_pathogenic	0.9049	pathogenic	-2.316	Highly Destabilizing	0.996	D	0.868	deleterious	None	None	None	None	N
I/E	0.8707	likely_pathogenic	0.8336	pathogenic	-2.095	Highly Destabilizing	0.988	D	0.861	deleterious	None	None	None	None	N
I/F	0.1752	likely_benign	0.1647	benign	-1.362	Destabilizing	0.968	D	0.743	deleterious	N	0.521569941	None	None	N
I/G	0.8362	likely_pathogenic	0.7825	pathogenic	-2.791	Highly Destabilizing	0.988	D	0.847	deleterious	None	None	None	None	N
I/H	0.7666	likely_pathogenic	0.7092	pathogenic	-2.094	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
I/K	0.7749	likely_pathogenic	0.7028	pathogenic	-1.713	Destabilizing	0.976	D	0.85	deleterious	None	None	None	None	N
I/L	0.1306	likely_benign	0.1277	benign	-0.788	Destabilizing	0.211	N	0.438	neutral	N	0.490588444	None	None	N
I/M	0.1228	likely_benign	0.1306	benign	-0.735	Destabilizing	0.64	D	0.499	neutral	N	0.511227594	None	None	N
I/N	0.6345	likely_pathogenic	0.5239	ambiguous	-2.019	Highly Destabilizing	0.984	D	0.863	deleterious	D	0.545968073	None	None	N
I/P	0.8989	likely_pathogenic	0.8498	pathogenic	-1.263	Destabilizing	0.996	D	0.866	deleterious	None	None	None	None	N
I/Q	0.7426	likely_pathogenic	0.6888	pathogenic	-1.882	Destabilizing	0.988	D	0.851	deleterious	None	None	None	None	N
I/R	0.7055	likely_pathogenic	0.6373	pathogenic	-1.484	Destabilizing	0.988	D	0.863	deleterious	None	None	None	None	N
I/S	0.5225	ambiguous	0.4446	ambiguous	-2.718	Highly Destabilizing	0.984	D	0.816	deleterious	D	0.545714584	None	None	N
I/T	0.4194	ambiguous	0.3421	ambiguous	-2.339	Highly Destabilizing	0.896	D	0.761	deleterious	N	0.518963049	None	None	N
I/V	0.0721	likely_benign	0.0685	benign	-1.263	Destabilizing	0.046	N	0.234	neutral	N	0.460110863	None	None	N
I/W	0.871	likely_pathogenic	0.8644	pathogenic	-1.639	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
I/Y	0.6107	likely_pathogenic	0.5581	ambiguous	-1.341	Destabilizing	0.988	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.