TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5295	16108;16109;16110	chr2:178733410;178733409;178733408	chr2:179598137;179598136;179598135
N2AB	4978	15157;15158;15159	chr2:178733410;178733409;178733408	chr2:179598137;179598136;179598135
N2A	4051	12376;12377;12378	chr2:178733410;178733409;178733408	chr2:179598137;179598136;179598135
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-36
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2021
• 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
Y/C	rs753916999	-1.09	0.978	D	0.609	0.427	0.47737504017	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
Y/C	rs753916999	-1.09	0.978	D	0.609	0.427	0.47737504017	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	2.28645E-05	None	0	0	None	0	0	0	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
Y/A	0.6394	likely_pathogenic	0.6917	pathogenic	-2.578	Highly Destabilizing	0.228	N	0.565	neutral	None	None	None	None	N
Y/C	0.1498	likely_benign	0.1945	benign	-1.042	Destabilizing	0.978	D	0.609	neutral	D	0.597200376	None	None	N
Y/D	0.5519	ambiguous	0.6098	pathogenic	-1.294	Destabilizing	0.794	D	0.639	neutral	D	0.556403774	None	None	N
Y/E	0.6955	likely_pathogenic	0.7488	pathogenic	-1.208	Destabilizing	0.418	N	0.602	neutral	None	None	None	None	N
Y/F	0.062	likely_benign	0.0657	benign	-1.187	Destabilizing	None	N	0.194	neutral	N	0.388189647	None	None	N
Y/G	0.6022	likely_pathogenic	0.6517	pathogenic	-2.911	Highly Destabilizing	0.593	D	0.626	neutral	None	None	None	None	N
Y/H	0.1607	likely_benign	0.1908	benign	-1.323	Destabilizing	0.794	D	0.563	neutral	N	0.490003076	None	None	N
Y/I	0.411	ambiguous	0.4215	ambiguous	-1.551	Destabilizing	0.264	N	0.554	neutral	None	None	None	None	N
Y/K	0.5563	ambiguous	0.5655	pathogenic	-1.298	Destabilizing	0.264	N	0.612	neutral	None	None	None	None	N
Y/L	0.326	likely_benign	0.3351	benign	-1.551	Destabilizing	0.129	N	0.489	neutral	None	None	None	None	N
Y/M	0.4334	ambiguous	0.4658	ambiguous	-1.085	Destabilizing	0.836	D	0.585	neutral	None	None	None	None	N
Y/N	0.2275	likely_benign	0.2462	benign	-1.552	Destabilizing	0.655	D	0.622	neutral	N	0.501927723	None	None	N
Y/P	0.9897	likely_pathogenic	0.9929	pathogenic	-1.891	Destabilizing	0.94	D	0.64	neutral	None	None	None	None	N
Y/Q	0.463	ambiguous	0.5156	ambiguous	-1.521	Destabilizing	0.716	D	0.599	neutral	None	None	None	None	N
Y/R	0.4287	ambiguous	0.4384	ambiguous	-0.79	Destabilizing	0.002	N	0.382	neutral	None	None	None	None	N
Y/S	0.3134	likely_benign	0.3465	ambiguous	-2.105	Highly Destabilizing	0.351	N	0.594	neutral	N	0.453657843	None	None	N
Y/T	0.5101	ambiguous	0.5491	ambiguous	-1.922	Destabilizing	0.593	D	0.585	neutral	None	None	None	None	N
Y/V	0.3591	ambiguous	0.373	ambiguous	-1.891	Destabilizing	0.264	N	0.559	neutral	None	None	None	None	N
Y/W	0.3675	ambiguous	0.4131	ambiguous	-0.748	Destabilizing	0.94	D	0.568	neutral	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.