TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16915	50968;50969;50970	chr2:178611486;178611485;178611484	chr2:179476213;179476212;179476211
N2AB	15274	46045;46046;46047	chr2:178611486;178611485;178611484	chr2:179476213;179476212;179476211
N2A	14347	43264;43265;43266	chr2:178611486;178611485;178611484	chr2:179476213;179476212;179476211
N2B	7850	23773;23774;23775	chr2:178611486;178611485;178611484	chr2:179476213;179476212;179476211
Novex-1	7975	24148;24149;24150	chr2:178611486;178611485;178611484	chr2:179476213;179476212;179476211
Novex-2	8042	24349;24350;24351	chr2:178611486;178611485;178611484	chr2:179476213;179476212;179476211
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: Fn3-11
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.4001
• 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/K	None	None	0.939	N	0.481	0.33	0.263140351381	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
E/A	0.2639	likely_benign	0.3041	benign	-0.67	Destabilizing	0.939	D	0.622	neutral	N	0.474043486	None	None	N
E/C	0.8922	likely_pathogenic	0.9453	pathogenic	-0.487	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
E/D	0.1413	likely_benign	0.1778	benign	-0.662	Destabilizing	0.02	N	0.171	neutral	N	0.396748022	None	None	N
E/F	0.8684	likely_pathogenic	0.9317	pathogenic	-0.177	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
E/G	0.2434	likely_benign	0.2948	benign	-0.961	Destabilizing	0.939	D	0.651	neutral	N	0.469321948	None	None	N
E/H	0.7106	likely_pathogenic	0.8026	pathogenic	-0.169	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
E/I	0.5841	likely_pathogenic	0.7005	pathogenic	0.1	Stabilizing	0.993	D	0.798	deleterious	None	None	None	None	N
E/K	0.3661	ambiguous	0.401	ambiguous	-0.455	Destabilizing	0.939	D	0.481	neutral	N	0.452181185	None	None	N
E/L	0.5657	likely_pathogenic	0.6777	pathogenic	0.1	Stabilizing	0.993	D	0.788	deleterious	None	None	None	None	N
E/M	0.6347	likely_pathogenic	0.7209	pathogenic	0.236	Stabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/N	0.385	ambiguous	0.4885	ambiguous	-0.788	Destabilizing	0.973	D	0.611	neutral	None	None	None	None	N
E/P	0.7098	likely_pathogenic	0.8229	pathogenic	-0.136	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
E/Q	0.2695	likely_benign	0.3067	benign	-0.692	Destabilizing	0.991	D	0.586	neutral	N	0.450475494	None	None	N
E/R	0.5146	ambiguous	0.5844	pathogenic	-0.071	Destabilizing	0.993	D	0.65	neutral	None	None	None	None	N
E/S	0.2986	likely_benign	0.3574	ambiguous	-1.045	Destabilizing	0.953	D	0.495	neutral	None	None	None	None	N
E/T	0.3394	likely_benign	0.4075	ambiguous	-0.814	Destabilizing	0.993	D	0.737	prob.delet.	None	None	None	None	N
E/V	0.3619	ambiguous	0.4429	ambiguous	-0.136	Destabilizing	0.991	D	0.773	deleterious	N	0.390726171	None	None	N
E/W	0.948	likely_pathogenic	0.9757	pathogenic	0.056	Stabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
E/Y	0.8085	likely_pathogenic	0.893	pathogenic	0.048	Stabilizing	0.999	D	0.777	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.