TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19804	59635;59636;59637	chr2:178592595;178592594;178592593	chr2:179457322;179457321;179457320
N2AB	18163	54712;54713;54714	chr2:178592595;178592594;178592593	chr2:179457322;179457321;179457320
N2A	17236	51931;51932;51933	chr2:178592595;178592594;178592593	chr2:179457322;179457321;179457320
N2B	10739	32440;32441;32442	chr2:178592595;178592594;178592593	chr2:179457322;179457321;179457320
Novex-1	10864	32815;32816;32817	chr2:178592595;178592594;178592593	chr2:179457322;179457321;179457320
Novex-2	10931	33016;33017;33018	chr2:178592595;178592594;178592593	chr2:179457322;179457321;179457320
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-119
• Domain position: 15
• Structural Position: 28
• Q(SASA): 0.1731
• 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
L/R	None	None	0.97	N	0.741	0.536	0.649577115175	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	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
L/A	0.9038	likely_pathogenic	0.9012	pathogenic	-2.752	Highly Destabilizing	0.86	D	0.66	neutral	None	None	None	None	N
L/C	0.8852	likely_pathogenic	0.8786	pathogenic	-2.042	Highly Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.9991	pathogenic	-3.218	Highly Destabilizing	0.993	D	0.796	deleterious	None	None	None	None	N
L/E	0.9925	likely_pathogenic	0.994	pathogenic	-2.987	Highly Destabilizing	0.978	D	0.803	deleterious	None	None	None	None	N
L/F	0.5882	likely_pathogenic	0.5574	ambiguous	-1.716	Destabilizing	0.915	D	0.703	prob.neutral	None	None	None	None	N
L/G	0.9872	likely_pathogenic	0.989	pathogenic	-3.295	Highly Destabilizing	0.978	D	0.791	deleterious	None	None	None	None	N
L/H	0.9779	likely_pathogenic	0.9818	pathogenic	-2.604	Highly Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
L/I	0.1564	likely_benign	0.1227	benign	-1.176	Destabilizing	0.058	N	0.247	neutral	N	0.425117563	None	None	N
L/K	0.9827	likely_pathogenic	0.9878	pathogenic	-2.388	Highly Destabilizing	0.978	D	0.775	deleterious	None	None	None	None	N
L/M	0.2893	likely_benign	0.2564	benign	-1.028	Destabilizing	0.978	D	0.66	neutral	None	None	None	None	N
L/N	0.992	likely_pathogenic	0.9935	pathogenic	-2.763	Highly Destabilizing	0.993	D	0.796	deleterious	None	None	None	None	N
L/P	0.9845	likely_pathogenic	0.9904	pathogenic	-1.684	Destabilizing	0.99	D	0.791	deleterious	N	0.491348101	None	None	N
L/Q	0.9623	likely_pathogenic	0.9684	pathogenic	-2.647	Highly Destabilizing	0.99	D	0.753	deleterious	N	0.502704406	None	None	N
L/R	0.9703	likely_pathogenic	0.9793	pathogenic	-1.991	Destabilizing	0.97	D	0.741	deleterious	N	0.502450917	None	None	N
L/S	0.9848	likely_pathogenic	0.9859	pathogenic	-3.428	Highly Destabilizing	0.978	D	0.76	deleterious	None	None	None	None	N
L/T	0.935	likely_pathogenic	0.9383	pathogenic	-3.046	Highly Destabilizing	0.926	D	0.747	deleterious	None	None	None	None	N
L/V	0.1865	likely_benign	0.1563	benign	-1.684	Destabilizing	0.489	N	0.563	neutral	N	0.452992023	None	None	N
L/W	0.9285	likely_pathogenic	0.9454	pathogenic	-2.07	Highly Destabilizing	0.043	N	0.565	neutral	None	None	None	None	N
L/Y	0.949	likely_pathogenic	0.9534	pathogenic	-1.803	Destabilizing	0.915	D	0.788	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.