TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21097	63514;63515;63516	chr2:178588118;178588117;178588116	chr2:179452845;179452844;179452843
N2AB	19456	58591;58592;58593	chr2:178588118;178588117;178588116	chr2:179452845;179452844;179452843
N2A	18529	55810;55811;55812	chr2:178588118;178588117;178588116	chr2:179452845;179452844;179452843
N2B	12032	36319;36320;36321	chr2:178588118;178588117;178588116	chr2:179452845;179452844;179452843
Novex-1	12157	36694;36695;36696	chr2:178588118;178588117;178588116	chr2:179452845;179452844;179452843
Novex-2	12224	36895;36896;36897	chr2:178588118;178588117;178588116	chr2:179452845;179452844;179452843
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: Fn3-41
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.6069
• 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/T	rs759579228	-0.684	0.942	N	0.635	0.306	0.635244795662	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
I/T	rs759579228	-0.684	0.942	N	0.635	0.306	0.635244795662	gnomAD-4.0.0	1.27456E-05	None	None	None	None	I	None	0	0	None	0	2.78443E-05	None	0	0	2.00317E-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
I/A	0.4255	ambiguous	0.3146	benign	-1.283	Destabilizing	0.86	D	0.524	neutral	None	None	None	None	I
I/C	0.8827	likely_pathogenic	0.812	pathogenic	-0.723	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	I
I/D	0.9303	likely_pathogenic	0.8789	pathogenic	-0.729	Destabilizing	0.993	D	0.815	deleterious	None	None	None	None	I
I/E	0.8168	likely_pathogenic	0.7292	pathogenic	-0.782	Destabilizing	0.978	D	0.817	deleterious	None	None	None	None	I
I/F	0.3268	likely_benign	0.2648	benign	-0.988	Destabilizing	0.89	D	0.658	neutral	N	0.488396629	None	None	I
I/G	0.8682	likely_pathogenic	0.7656	pathogenic	-1.535	Destabilizing	0.978	D	0.815	deleterious	None	None	None	None	I
I/H	0.8052	likely_pathogenic	0.7046	pathogenic	-0.709	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	I
I/K	0.6561	likely_pathogenic	0.5503	ambiguous	-0.827	Destabilizing	0.978	D	0.816	deleterious	None	None	None	None	I
I/L	0.1634	likely_benign	0.1306	benign	-0.7	Destabilizing	0.006	N	0.143	neutral	N	0.453312602	None	None	I
I/M	0.1629	likely_benign	0.13	benign	-0.504	Destabilizing	0.942	D	0.645	neutral	N	0.472520874	None	None	I
I/N	0.6735	likely_pathogenic	0.5505	ambiguous	-0.567	Destabilizing	0.99	D	0.819	deleterious	N	0.469531906	None	None	I
I/P	0.9519	likely_pathogenic	0.912	pathogenic	-0.861	Destabilizing	0.993	D	0.82	deleterious	None	None	None	None	I
I/Q	0.723	likely_pathogenic	0.5941	pathogenic	-0.813	Destabilizing	0.993	D	0.817	deleterious	None	None	None	None	I
I/R	0.5418	ambiguous	0.4398	ambiguous	-0.163	Destabilizing	0.978	D	0.82	deleterious	None	None	None	None	I
I/S	0.5184	ambiguous	0.3812	ambiguous	-1.104	Destabilizing	0.971	D	0.711	prob.delet.	N	0.484731588	None	None	I
I/T	0.1517	likely_benign	0.1252	benign	-1.05	Destabilizing	0.942	D	0.635	neutral	N	0.408577603	None	None	I
I/V	0.137	likely_benign	0.1184	benign	-0.861	Destabilizing	0.294	N	0.325	neutral	N	0.493793788	None	None	I
I/W	0.8727	likely_pathogenic	0.821	pathogenic	-0.996	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	I
I/Y	0.7957	likely_pathogenic	0.695	pathogenic	-0.793	Destabilizing	0.978	D	0.721	prob.delet.	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.