TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6436	19531;19532;19533	chr2:178728620;178728619;178728618	chr2:179593347;179593346;179593345
N2AB	6119	18580;18581;18582	chr2:178728620;178728619;178728618	chr2:179593347;179593346;179593345
N2A	5192	15799;15800;15801	chr2:178728620;178728619;178728618	chr2:179593347;179593346;179593345
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-48
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.7152
• 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
E/A	rs778366508	-0.2	0.896	D	0.434	0.283	0.413891365518	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
E/A	rs778366508	-0.2	0.896	D	0.434	0.283	0.413891365518	gnomAD-4.0.0	1.59258E-06	None	None	None	None	N	None	0	0	None	0	2.78056E-05	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
E/A	0.2385	likely_benign	0.2074	benign	-0.502	Destabilizing	0.896	D	0.434	neutral	D	0.533944979	None	None	N
E/C	0.9043	likely_pathogenic	0.8709	pathogenic	-0.19	Destabilizing	0.999	D	0.537	neutral	None	None	None	None	N
E/D	0.162	likely_benign	0.1337	benign	-0.285	Destabilizing	0.026	N	0.21	neutral	N	0.485132311	None	None	N
E/F	0.8096	likely_pathogenic	0.7764	pathogenic	-0.223	Destabilizing	0.988	D	0.52	neutral	None	None	None	None	N
E/G	0.2706	likely_benign	0.2016	benign	-0.699	Destabilizing	0.896	D	0.464	neutral	N	0.501411273	None	None	N
E/H	0.4685	ambiguous	0.4254	ambiguous	0.104	Stabilizing	0.999	D	0.356	neutral	None	None	None	None	N
E/I	0.3916	ambiguous	0.3706	ambiguous	-0.014	Destabilizing	0.261	N	0.383	neutral	None	None	None	None	N
E/K	0.1615	likely_benign	0.1277	benign	0.356	Stabilizing	0.896	D	0.425	neutral	N	0.460735299	None	None	N
E/L	0.4464	ambiguous	0.4379	ambiguous	-0.014	Destabilizing	0.851	D	0.469	neutral	None	None	None	None	N
E/M	0.5483	ambiguous	0.5171	ambiguous	0.036	Stabilizing	0.997	D	0.506	neutral	None	None	None	None	N
E/N	0.3412	ambiguous	0.286	benign	-0.152	Destabilizing	0.952	D	0.358	neutral	None	None	None	None	N
E/P	0.9095	likely_pathogenic	0.8732	pathogenic	-0.158	Destabilizing	0.988	D	0.434	neutral	None	None	None	None	N
E/Q	0.133	likely_benign	0.1254	benign	-0.082	Destabilizing	0.984	D	0.375	neutral	N	0.507547811	None	None	N
E/R	0.2507	likely_benign	0.2113	benign	0.591	Stabilizing	0.988	D	0.366	neutral	None	None	None	None	N
E/S	0.2729	likely_benign	0.2368	benign	-0.274	Destabilizing	0.851	D	0.384	neutral	None	None	None	None	N
E/T	0.2945	likely_benign	0.2505	benign	-0.096	Destabilizing	0.132	N	0.223	neutral	None	None	None	None	N
E/V	0.2592	likely_benign	0.2343	benign	-0.158	Destabilizing	0.811	D	0.465	neutral	N	0.492637074	None	None	N
E/W	0.9023	likely_pathogenic	0.8754	pathogenic	-0.002	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
E/Y	0.6866	likely_pathogenic	0.629	pathogenic	0.033	Stabilizing	0.996	D	0.509	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.