TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31239	93940;93941;93942	chr2:178547911;178547910;178547909	chr2:179412638;179412637;179412636
N2AB	29598	89017;89018;89019	chr2:178547911;178547910;178547909	chr2:179412638;179412637;179412636
N2A	28671	86236;86237;86238	chr2:178547911;178547910;178547909	chr2:179412638;179412637;179412636
N2B	22174	66745;66746;66747	chr2:178547911;178547910;178547909	chr2:179412638;179412637;179412636
Novex-1	22299	67120;67121;67122	chr2:178547911;178547910;178547909	chr2:179412638;179412637;179412636
Novex-2	22366	67321;67322;67323	chr2:178547911;178547910;178547909	chr2:179412638;179412637;179412636
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-151
• Domain position: 22
• Structural Position: 35
• Q(SASA): 0.1468
• Predicted PPI site: I

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/N	None	None	0.999	D	0.833	0.685	0.819228050113	gnomAD-4.0.0	1.36838E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79887E-06	0	0
I/V	None	None	0.941	N	0.457	0.163	0.400468435593	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-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	0.8336	likely_pathogenic	0.8802	pathogenic	-2.049	Highly Destabilizing	0.996	D	0.69	prob.neutral	None	None	None	None	I
I/C	0.8583	likely_pathogenic	0.888	pathogenic	-1.447	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
I/D	0.996	likely_pathogenic	0.9974	pathogenic	-1.269	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
I/E	0.9889	likely_pathogenic	0.992	pathogenic	-1.194	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
I/F	0.2559	likely_benign	0.2686	benign	-1.355	Destabilizing	0.978	D	0.661	neutral	N	0.489311554	None	None	I
I/G	0.9722	likely_pathogenic	0.9833	pathogenic	-2.458	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
I/H	0.9535	likely_pathogenic	0.9656	pathogenic	-1.62	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
I/K	0.9637	likely_pathogenic	0.9726	pathogenic	-1.471	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
I/L	0.1866	likely_benign	0.2082	benign	-0.957	Destabilizing	0.973	D	0.445	neutral	D	0.52884859	None	None	I
I/M	0.2467	likely_benign	0.2654	benign	-0.815	Destabilizing	0.999	D	0.683	prob.neutral	N	0.50036136	None	None	I
I/N	0.9535	likely_pathogenic	0.9689	pathogenic	-1.405	Destabilizing	0.999	D	0.833	deleterious	D	0.52358095	None	None	I
I/P	0.9871	likely_pathogenic	0.9902	pathogenic	-1.291	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
I/Q	0.9666	likely_pathogenic	0.9755	pathogenic	-1.467	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
I/R	0.9398	likely_pathogenic	0.9531	pathogenic	-0.96	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
I/S	0.9004	likely_pathogenic	0.9341	pathogenic	-2.151	Highly Destabilizing	0.998	D	0.799	deleterious	N	0.50061485	None	None	I
I/T	0.8416	likely_pathogenic	0.8903	pathogenic	-1.935	Destabilizing	0.998	D	0.771	deleterious	N	0.503702268	None	None	I
I/V	0.075	likely_benign	0.0793	benign	-1.291	Destabilizing	0.941	D	0.457	neutral	N	0.450491302	None	None	I
I/W	0.9362	likely_pathogenic	0.9481	pathogenic	-1.448	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
I/Y	0.7182	likely_pathogenic	0.76	pathogenic	-1.232	Destabilizing	0.611	D	0.469	neutral	None	None	None	None	I

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.