TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8417	25474;25475;25476	chr2:178717625;178717624;178717623	chr2:179582352;179582351;179582350
N2AB	8100	24523;24524;24525	chr2:178717625;178717624;178717623	chr2:179582352;179582351;179582350
N2A	7173	21742;21743;21744	chr2:178717625;178717624;178717623	chr2:179582352;179582351;179582350
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-69
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.061
• 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	rs774234445	-1.504	0.999	D	0.79	0.535	0.7142813	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
L/F	rs774234445	-1.504	0.999	D	0.79	0.535	0.7142813	gnomAD-4.0.0	4.7774E-06	None	None	None	None	N	None	0	2.28802E-05	None	0	0	None	0	0	2.85989E-06	0	3.027E-05

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	0.9366	likely_pathogenic	0.9121	pathogenic	-2.134	Highly Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
L/C	0.949	likely_pathogenic	0.9258	pathogenic	-1.555	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9996	pathogenic	-2.993	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
L/E	0.997	likely_pathogenic	0.9958	pathogenic	-2.673	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/F	0.6722	likely_pathogenic	0.5841	pathogenic	-1.334	Destabilizing	0.999	D	0.79	deleterious	D	0.539298	None	None	N
L/G	0.9897	likely_pathogenic	0.984	pathogenic	-2.721	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/H	0.9905	likely_pathogenic	0.9857	pathogenic	-2.748	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.5521752	None	None	N
L/I	0.3044	likely_benign	0.2661	benign	-0.367	Destabilizing	0.243	N	0.388	neutral	N	0.5115325	None	None	N
L/K	0.994	likely_pathogenic	0.9928	pathogenic	-1.579	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/M	0.3756	ambiguous	0.311	benign	-0.706	Destabilizing	0.997	D	0.786	deleterious	None	None	None	None	N
L/N	0.997	likely_pathogenic	0.9958	pathogenic	-2.333	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/P	0.9982	likely_pathogenic	0.9975	pathogenic	-0.948	Destabilizing	1.0	D	0.905	deleterious	D	0.5635315	None	None	N
L/Q	0.9813	likely_pathogenic	0.972	pathogenic	-1.912	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/R	0.9853	likely_pathogenic	0.9799	pathogenic	-1.926	Destabilizing	1.0	D	0.899	deleterious	D	0.5635315	None	None	N
L/S	0.9909	likely_pathogenic	0.9857	pathogenic	-2.793	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/T	0.9751	likely_pathogenic	0.9653	pathogenic	-2.299	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/V	0.3484	ambiguous	0.2884	benign	-0.948	Destabilizing	0.923	D	0.748	deleterious	D	0.5239028	None	None	N
L/W	0.9725	likely_pathogenic	0.9578	pathogenic	-1.735	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/Y	0.9732	likely_pathogenic	0.9638	pathogenic	-1.484	Destabilizing	1.0	D	0.842	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.