TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32800	98623;98624;98625	chr2:178539667;178539666;178539665	chr2:179404394;179404393;179404392
N2AB	31159	93700;93701;93702	chr2:178539667;178539666;178539665	chr2:179404394;179404393;179404392
N2A	30232	90919;90920;90921	chr2:178539667;178539666;178539665	chr2:179404394;179404393;179404392
N2B	23735	71428;71429;71430	chr2:178539667;178539666;178539665	chr2:179404394;179404393;179404392
Novex-1	23860	71803;71804;71805	chr2:178539667;178539666;178539665	chr2:179404394;179404393;179404392
Novex-2	23927	72004;72005;72006	chr2:178539667;178539666;178539665	chr2:179404394;179404393;179404392
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-127
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.0826
• 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
E/K	None	None	0.992	N	0.651	0.295	0.319686207203	gnomAD-4.0.0	1.08029E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18125E-05	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
E/A	0.2271	likely_benign	0.2363	benign	-0.752	Destabilizing	0.996	D	0.653	neutral	N	0.488358178	None	None	N
E/C	0.8624	likely_pathogenic	0.8788	pathogenic	-0.446	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/D	0.4302	ambiguous	0.4118	ambiguous	-1.025	Destabilizing	0.996	D	0.629	neutral	N	0.45965536	None	None	N
E/F	0.8981	likely_pathogenic	0.9083	pathogenic	-0.181	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
E/G	0.3754	ambiguous	0.3706	ambiguous	-1.107	Destabilizing	0.999	D	0.756	deleterious	N	0.484029793	None	None	N
E/H	0.7438	likely_pathogenic	0.762	pathogenic	-0.415	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/I	0.4514	ambiguous	0.4934	ambiguous	0.212	Stabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/K	0.2674	likely_benign	0.2964	benign	-0.531	Destabilizing	0.992	D	0.651	neutral	N	0.486934026	None	None	N
E/L	0.5396	ambiguous	0.5778	pathogenic	0.212	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/M	0.5791	likely_pathogenic	0.613	pathogenic	0.536	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
E/N	0.6112	likely_pathogenic	0.6184	pathogenic	-1.011	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/P	0.9471	likely_pathogenic	0.9546	pathogenic	-0.088	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/Q	0.1853	likely_benign	0.1969	benign	-0.877	Destabilizing	0.957	D	0.357	neutral	N	0.463846522	None	None	N
E/R	0.3867	ambiguous	0.4235	ambiguous	-0.237	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
E/S	0.3432	ambiguous	0.3433	ambiguous	-1.287	Destabilizing	0.997	D	0.651	neutral	None	None	None	None	N
E/T	0.3481	ambiguous	0.3566	ambiguous	-0.995	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/V	0.2575	likely_benign	0.2815	benign	-0.088	Destabilizing	0.999	D	0.763	deleterious	N	0.440084228	None	None	N
E/W	0.9685	likely_pathogenic	0.9724	pathogenic	0.064	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/Y	0.8465	likely_pathogenic	0.8614	pathogenic	0.065	Stabilizing	1.0	D	0.848	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.