TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30234	90925;90926;90927	chr2:178552200;178552199;178552198	chr2:179416927;179416926;179416925
N2AB	28593	86002;86003;86004	chr2:178552200;178552199;178552198	chr2:179416927;179416926;179416925
N2A	27666	83221;83222;83223	chr2:178552200;178552199;178552198	chr2:179416927;179416926;179416925
N2B	21169	63730;63731;63732	chr2:178552200;178552199;178552198	chr2:179416927;179416926;179416925
Novex-1	21294	64105;64106;64107	chr2:178552200;178552199;178552198	chr2:179416927;179416926;179416925
Novex-2	21361	64306;64307;64308	chr2:178552200;178552199;178552198	chr2:179416927;179416926;179416925
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-108
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.2228
• 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
F/I	None	None	0.026	N	0.381	0.174	0.162503812791	gnomAD-4.0.0	1.59165E-06	None	None	None	None	I	None	0	0	None	0	2.77331E-05	None	0	0	0	0	0
F/S	None	None	0.984	N	0.743	0.528	0.764471569041	gnomAD-4.0.0	1.59168E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85876E-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
F/A	0.5713	likely_pathogenic	0.5974	pathogenic	-2.357	Highly Destabilizing	0.919	D	0.672	neutral	None	None	None	None	I
F/C	0.2909	likely_benign	0.3164	benign	-1.912	Destabilizing	0.999	D	0.749	deleterious	N	0.499397183	None	None	I
F/D	0.9433	likely_pathogenic	0.9525	pathogenic	-1.08	Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	I
F/E	0.9201	likely_pathogenic	0.9304	pathogenic	-0.908	Destabilizing	0.996	D	0.808	deleterious	None	None	None	None	I
F/G	0.8676	likely_pathogenic	0.8674	pathogenic	-2.77	Highly Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	I
F/H	0.7935	likely_pathogenic	0.7982	pathogenic	-1.138	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
F/I	0.1609	likely_benign	0.197	benign	-1.069	Destabilizing	0.026	N	0.381	neutral	N	0.408985822	None	None	I
F/K	0.9186	likely_pathogenic	0.9271	pathogenic	-1.71	Destabilizing	0.988	D	0.807	deleterious	None	None	None	None	I
F/L	0.7041	likely_pathogenic	0.7604	pathogenic	-1.069	Destabilizing	0.026	N	0.215	neutral	N	0.456835697	None	None	I
F/M	0.3656	ambiguous	0.3925	ambiguous	-1.067	Destabilizing	0.976	D	0.569	neutral	None	None	None	None	I
F/N	0.8394	likely_pathogenic	0.8576	pathogenic	-1.928	Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	I
F/P	0.908	likely_pathogenic	0.9369	pathogenic	-1.498	Destabilizing	0.996	D	0.812	deleterious	None	None	None	None	I
F/Q	0.8742	likely_pathogenic	0.8793	pathogenic	-1.833	Destabilizing	0.996	D	0.81	deleterious	None	None	None	None	I
F/R	0.8817	likely_pathogenic	0.8945	pathogenic	-1.256	Destabilizing	0.988	D	0.819	deleterious	None	None	None	None	I
F/S	0.656	likely_pathogenic	0.6698	pathogenic	-2.847	Highly Destabilizing	0.984	D	0.743	deleterious	N	0.493742682	None	None	I
F/T	0.5375	ambiguous	0.5708	pathogenic	-2.563	Highly Destabilizing	0.976	D	0.731	prob.delet.	None	None	None	None	I
F/V	0.1912	likely_benign	0.2212	benign	-1.498	Destabilizing	0.64	D	0.61	neutral	N	0.393744224	None	None	I
F/W	0.5047	ambiguous	0.5174	ambiguous	-0.089	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	I
F/Y	0.2617	likely_benign	0.2647	benign	-0.444	Destabilizing	0.946	D	0.612	neutral	N	0.509536818	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.