TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17079	51460;51461;51462	chr2:178610291;178610290;178610289	chr2:179475018;179475017;179475016
N2AB	15438	46537;46538;46539	chr2:178610291;178610290;178610289	chr2:179475018;179475017;179475016
N2A	14511	43756;43757;43758	chr2:178610291;178610290;178610289	chr2:179475018;179475017;179475016
N2B	8014	24265;24266;24267	chr2:178610291;178610290;178610289	chr2:179475018;179475017;179475016
Novex-1	8139	24640;24641;24642	chr2:178610291;178610290;178610289	chr2:179475018;179475017;179475016
Novex-2	8206	24841;24842;24843	chr2:178610291;178610290;178610289	chr2:179475018;179475017;179475016
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: Fn3-12
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2112
• 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/V	None	None	0.4	N	0.228	0.104	0.455265801863	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	6.33473E-05	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	0.9779	likely_pathogenic	0.9764	pathogenic	-2.546	Highly Destabilizing	0.985	D	0.701	prob.neutral	None	None	None	None	I
I/C	0.9793	likely_pathogenic	0.9805	pathogenic	-1.618	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
I/D	0.9991	likely_pathogenic	0.9991	pathogenic	-2.894	Highly Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	I
I/E	0.9969	likely_pathogenic	0.9969	pathogenic	-2.75	Highly Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	I
I/F	0.9396	likely_pathogenic	0.9365	pathogenic	-1.643	Destabilizing	0.994	D	0.691	prob.neutral	D	0.651955182	None	None	I
I/G	0.9974	likely_pathogenic	0.9973	pathogenic	-3.012	Highly Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	I
I/H	0.9974	likely_pathogenic	0.9971	pathogenic	-2.446	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
I/K	0.995	likely_pathogenic	0.9946	pathogenic	-2.009	Highly Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	I
I/L	0.3858	ambiguous	0.3923	ambiguous	-1.226	Destabilizing	0.061	N	0.208	neutral	D	0.527551732	None	None	I
I/M	0.6678	likely_pathogenic	0.6705	pathogenic	-0.924	Destabilizing	0.994	D	0.687	prob.neutral	D	0.716566744	None	None	I
I/N	0.9826	likely_pathogenic	0.9833	pathogenic	-2.135	Highly Destabilizing	0.999	D	0.843	deleterious	D	0.718643762	None	None	I
I/P	0.9837	likely_pathogenic	0.9789	pathogenic	-1.645	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	I
I/Q	0.9956	likely_pathogenic	0.9949	pathogenic	-2.137	Highly Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	I
I/R	0.9928	likely_pathogenic	0.9921	pathogenic	-1.5	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	I
I/S	0.9845	likely_pathogenic	0.9841	pathogenic	-2.747	Highly Destabilizing	0.997	D	0.805	deleterious	D	0.69494957	None	None	I
I/T	0.9571	likely_pathogenic	0.9645	pathogenic	-2.483	Highly Destabilizing	0.98	D	0.769	deleterious	D	0.656921779	None	None	I
I/V	0.086	likely_benign	0.0973	benign	-1.645	Destabilizing	0.4	N	0.228	neutral	N	0.484952299	None	None	I
I/W	0.9991	likely_pathogenic	0.9989	pathogenic	-2.036	Highly Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
I/Y	0.9935	likely_pathogenic	0.9932	pathogenic	-1.79	Destabilizing	0.999	D	0.772	deleterious	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.