TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3021	9286;9287;9288	chr2:178768775;178768774;178768773	chr2:179633502;179633501;179633500
N2AB	3021	9286;9287;9288	chr2:178768775;178768774;178768773	chr2:179633502;179633501;179633500
N2A	3021	9286;9287;9288	chr2:178768775;178768774;178768773	chr2:179633502;179633501;179633500
N2B	2975	9148;9149;9150	chr2:178768775;178768774;178768773	chr2:179633502;179633501;179633500
Novex-1	2975	9148;9149;9150	chr2:178768775;178768774;178768773	chr2:179633502;179633501;179633500
Novex-2	2975	9148;9149;9150	chr2:178768775;178768774;178768773	chr2:179633502;179633501;179633500
Novex-3	3021	9286;9287;9288	chr2:178768775;178768774;178768773	chr2:179633502;179633501;179633500

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-20
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.2055
• 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
L/F	None	None	0.991	N	0.678	0.197	0.571034400148	gnomAD-4.0.0	1.5906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
L/A	0.4772	ambiguous	0.5296	ambiguous	-1.758	Destabilizing	0.953	D	0.555	neutral	None	None	None	None	N
L/C	0.5727	likely_pathogenic	0.6467	pathogenic	-0.828	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
L/D	0.7911	likely_pathogenic	0.8312	pathogenic	-1.628	Destabilizing	0.986	D	0.754	deleterious	None	None	None	None	N
L/E	0.5831	likely_pathogenic	0.6417	pathogenic	-1.653	Destabilizing	0.973	D	0.727	prob.delet.	None	None	None	None	N
L/F	0.1382	likely_benign	0.1744	benign	-1.425	Destabilizing	0.991	D	0.678	prob.neutral	N	0.494406951	None	None	N
L/G	0.5975	likely_pathogenic	0.6355	pathogenic	-2.059	Highly Destabilizing	0.986	D	0.761	deleterious	None	None	None	None	N
L/H	0.2525	likely_benign	0.3026	benign	-1.392	Destabilizing	0.998	D	0.729	prob.delet.	N	0.504327812	None	None	N
L/I	0.2372	likely_benign	0.2929	benign	-1.003	Destabilizing	0.322	N	0.183	neutral	N	0.505384125	None	None	N
L/K	0.31	likely_benign	0.3566	ambiguous	-1.215	Destabilizing	0.973	D	0.712	prob.delet.	None	None	None	None	N
L/M	0.1227	likely_benign	0.1409	benign	-0.575	Destabilizing	0.993	D	0.652	neutral	None	None	None	None	N
L/N	0.381	ambiguous	0.4199	ambiguous	-0.966	Destabilizing	0.986	D	0.755	deleterious	None	None	None	None	N
L/P	0.8468	likely_pathogenic	0.873	pathogenic	-1.225	Destabilizing	0.991	D	0.756	deleterious	N	0.506132055	None	None	N
L/Q	0.1884	likely_benign	0.2116	benign	-1.215	Destabilizing	0.591	D	0.508	neutral	None	None	None	None	N
L/R	0.236	likely_benign	0.2708	benign	-0.539	Destabilizing	0.964	D	0.739	prob.delet.	N	0.439258229	None	None	N
L/S	0.4405	ambiguous	0.5092	ambiguous	-1.466	Destabilizing	0.986	D	0.683	prob.neutral	None	None	None	None	N
L/T	0.377	ambiguous	0.4327	ambiguous	-1.39	Destabilizing	0.986	D	0.637	neutral	None	None	None	None	N
L/V	0.2235	likely_benign	0.2716	benign	-1.225	Destabilizing	0.76	D	0.541	neutral	N	0.493384545	None	None	N
L/W	0.2854	likely_benign	0.3234	benign	-1.536	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
L/Y	0.2646	likely_benign	0.3123	benign	-1.318	Destabilizing	0.998	D	0.701	prob.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.