TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31798	95617;95618;95619	chr2:178545844;178545843;178545842	chr2:179410571;179410570;179410569
N2AB	30157	90694;90695;90696	chr2:178545844;178545843;178545842	chr2:179410571;179410570;179410569
N2A	29230	87913;87914;87915	chr2:178545844;178545843;178545842	chr2:179410571;179410570;179410569
N2B	22733	68422;68423;68424	chr2:178545844;178545843;178545842	chr2:179410571;179410570;179410569
Novex-1	22858	68797;68798;68799	chr2:178545844;178545843;178545842	chr2:179410571;179410570;179410569
Novex-2	22925	68998;68999;69000	chr2:178545844;178545843;178545842	chr2:179410571;179410570;179410569
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-119
• Domain position: 91
• Structural Position: 126
• Q(SASA): 0.5183
• 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
P/A	None	None	0.002	N	0.308	0.159	0.128392430309	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
P/A	0.0622	likely_benign	0.066	benign	-0.758	Destabilizing	0.002	N	0.308	neutral	N	0.498520109	None	None	N
P/C	0.4089	ambiguous	0.4484	ambiguous	-0.67	Destabilizing	0.992	D	0.822	deleterious	None	None	None	None	N
P/D	0.5465	ambiguous	0.593	pathogenic	-0.669	Destabilizing	0.848	D	0.617	neutral	None	None	None	None	N
P/E	0.3244	likely_benign	0.3576	ambiguous	-0.743	Destabilizing	0.615	D	0.593	neutral	None	None	None	None	N
P/F	0.5829	likely_pathogenic	0.6063	pathogenic	-0.728	Destabilizing	0.919	D	0.824	deleterious	None	None	None	None	N
P/G	0.2722	likely_benign	0.3049	benign	-0.959	Destabilizing	0.444	N	0.645	neutral	None	None	None	None	N
P/H	0.3012	likely_benign	0.3131	benign	-0.456	Destabilizing	0.977	D	0.775	deleterious	None	None	None	None	N
P/I	0.3123	likely_benign	0.3371	benign	-0.353	Destabilizing	0.848	D	0.774	deleterious	None	None	None	None	N
P/K	0.3757	ambiguous	0.4063	ambiguous	-0.77	Destabilizing	0.444	N	0.601	neutral	None	None	None	None	N
P/L	0.1862	likely_benign	0.2005	benign	-0.353	Destabilizing	0.376	N	0.715	prob.delet.	N	0.507822736	None	None	N
P/M	0.3154	likely_benign	0.3447	ambiguous	-0.397	Destabilizing	0.992	D	0.777	deleterious	None	None	None	None	N
P/N	0.3458	ambiguous	0.3782	ambiguous	-0.522	Destabilizing	0.737	D	0.676	prob.neutral	None	None	None	None	N
P/Q	0.2204	likely_benign	0.2382	benign	-0.742	Destabilizing	0.808	D	0.677	prob.neutral	D	0.526812364	None	None	N
P/R	0.2915	likely_benign	0.3104	benign	-0.205	Destabilizing	0.808	D	0.732	deleterious	N	0.518672063	None	None	N
P/S	0.1348	likely_benign	0.1446	benign	-0.898	Destabilizing	0.016	N	0.352	neutral	N	0.485778007	None	None	N
P/T	0.1175	likely_benign	0.131	benign	-0.87	Destabilizing	0.016	N	0.352	neutral	N	0.5031747	None	None	N
P/V	0.1981	likely_benign	0.2182	benign	-0.452	Destabilizing	0.444	N	0.653	prob.neutral	None	None	None	None	N
P/W	0.7444	likely_pathogenic	0.7649	pathogenic	-0.848	Destabilizing	0.992	D	0.775	deleterious	None	None	None	None	N
P/Y	0.5383	ambiguous	0.5534	ambiguous	-0.562	Destabilizing	0.972	D	0.823	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.