TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5381	16366;16367;16368	chr2:178733035;178733034;178733033	chr2:179597762;179597761;179597760
N2AB	5064	15415;15416;15417	chr2:178733035;178733034;178733033	chr2:179597762;179597761;179597760
N2A	4137	12634;12635;12636	chr2:178733035;178733034;178733033	chr2:179597762;179597761;179597760
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-37
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.1726
• 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
A/S	None	None	0.079	N	0.255	0.137	0.39162414616	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
A/C	0.6668	likely_pathogenic	0.5671	pathogenic	-0.607	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
A/D	0.6809	likely_pathogenic	0.5384	ambiguous	-0.259	Destabilizing	0.986	D	0.567	neutral	None	None	None	None	N
A/E	0.5899	likely_pathogenic	0.4578	ambiguous	-0.319	Destabilizing	0.939	D	0.565	neutral	N	0.414210789	None	None	N
A/F	0.5234	ambiguous	0.4312	ambiguous	-0.633	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
A/G	0.2173	likely_benign	0.1849	benign	-0.62	Destabilizing	0.76	D	0.483	neutral	N	0.446248636	None	None	N
A/H	0.6757	likely_pathogenic	0.571	pathogenic	-0.649	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
A/I	0.4348	ambiguous	0.3275	benign	-0.054	Destabilizing	0.993	D	0.62	neutral	None	None	None	None	N
A/K	0.7608	likely_pathogenic	0.6398	pathogenic	-0.695	Destabilizing	0.953	D	0.557	neutral	None	None	None	None	N
A/L	0.3155	likely_benign	0.2435	benign	-0.054	Destabilizing	0.953	D	0.554	neutral	None	None	None	None	N
A/M	0.3503	ambiguous	0.2745	benign	-0.206	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
A/N	0.4746	ambiguous	0.3731	ambiguous	-0.412	Destabilizing	0.986	D	0.572	neutral	None	None	None	None	N
A/P	0.9341	likely_pathogenic	0.8999	pathogenic	-0.136	Destabilizing	0.991	D	0.62	neutral	N	0.484758185	None	None	N
A/Q	0.5386	ambiguous	0.456	ambiguous	-0.544	Destabilizing	0.993	D	0.644	neutral	None	None	None	None	N
A/R	0.6486	likely_pathogenic	0.5315	ambiguous	-0.392	Destabilizing	0.986	D	0.631	neutral	None	None	None	None	N
A/S	0.1015	likely_benign	0.0865	benign	-0.76	Destabilizing	0.079	N	0.255	neutral	N	0.399377409	None	None	N
A/T	0.1211	likely_benign	0.0859	benign	-0.712	Destabilizing	0.885	D	0.454	neutral	N	0.434740776	None	None	N
A/V	0.2296	likely_benign	0.1704	benign	-0.136	Destabilizing	0.939	D	0.531	neutral	N	0.460447297	None	None	N
A/W	0.8809	likely_pathogenic	0.8138	pathogenic	-0.922	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
A/Y	0.6963	likely_pathogenic	0.5876	pathogenic	-0.499	Destabilizing	0.998	D	0.655	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.