TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17006	51241;51242;51243	chr2:178611113;178611112;178611111	chr2:179475840;179475839;179475838
N2AB	15365	46318;46319;46320	chr2:178611113;178611112;178611111	chr2:179475840;179475839;179475838
N2A	14438	43537;43538;43539	chr2:178611113;178611112;178611111	chr2:179475840;179475839;179475838
N2B	7941	24046;24047;24048	chr2:178611113;178611112;178611111	chr2:179475840;179475839;179475838
Novex-1	8066	24421;24422;24423	chr2:178611113;178611112;178611111	chr2:179475840;179475839;179475838
Novex-2	8133	24622;24623;24624	chr2:178611113;178611112;178611111	chr2:179475840;179475839;179475838
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-111
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.5642
• 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
D/V	None	None	0.942	N	0.643	0.408	0.653256221078	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
D/A	0.2542	likely_benign	0.2765	benign	-0.612	Destabilizing	0.698	D	0.482	neutral	N	0.511563129	None	None	N
D/C	0.6566	likely_pathogenic	0.6709	pathogenic	-0.29	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	N
D/E	0.209	likely_benign	0.2093	benign	-0.542	Destabilizing	0.006	N	0.125	neutral	N	0.451134931	None	None	N
D/F	0.6869	likely_pathogenic	0.7063	pathogenic	-0.264	Destabilizing	0.998	D	0.606	neutral	None	None	None	None	N
D/G	0.1995	likely_benign	0.2153	benign	-0.911	Destabilizing	0.822	D	0.511	neutral	N	0.50078845	None	None	N
D/H	0.3457	ambiguous	0.3588	ambiguous	-0.416	Destabilizing	0.992	D	0.544	neutral	N	0.510501615	None	None	N
D/I	0.4641	ambiguous	0.4859	ambiguous	0.165	Stabilizing	0.978	D	0.63	neutral	None	None	None	None	N
D/K	0.4413	ambiguous	0.4812	ambiguous	-0.518	Destabilizing	0.754	D	0.511	neutral	None	None	None	None	N
D/L	0.4546	ambiguous	0.4764	ambiguous	0.165	Stabilizing	0.956	D	0.646	neutral	None	None	None	None	N
D/M	0.7004	likely_pathogenic	0.7112	pathogenic	0.51	Stabilizing	0.998	D	0.603	neutral	None	None	None	None	N
D/N	0.1051	likely_benign	0.1149	benign	-0.816	Destabilizing	0.822	D	0.443	neutral	N	0.494283936	None	None	N
D/P	0.8573	likely_pathogenic	0.8716	pathogenic	-0.071	Destabilizing	0.978	D	0.584	neutral	None	None	None	None	N
D/Q	0.4002	ambiguous	0.4141	ambiguous	-0.695	Destabilizing	0.915	D	0.486	neutral	None	None	None	None	N
D/R	0.48	ambiguous	0.5084	ambiguous	-0.238	Destabilizing	0.956	D	0.616	neutral	None	None	None	None	N
D/S	0.143	likely_benign	0.1512	benign	-1.027	Destabilizing	0.754	D	0.411	neutral	None	None	None	None	N
D/T	0.2693	likely_benign	0.286	benign	-0.795	Destabilizing	0.956	D	0.514	neutral	None	None	None	None	N
D/V	0.3065	likely_benign	0.3316	benign	-0.071	Destabilizing	0.942	D	0.643	neutral	N	0.511897292	None	None	N
D/W	0.9152	likely_pathogenic	0.9179	pathogenic	-0.088	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
D/Y	0.3107	likely_benign	0.3426	ambiguous	-0.061	Destabilizing	0.997	D	0.607	neutral	N	0.505665242	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.