TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17771	53536;53537;53538	chr2:178607291;178607290;178607289	chr2:179472018;179472017;179472016
N2AB	16130	48613;48614;48615	chr2:178607291;178607290;178607289	chr2:179472018;179472017;179472016
N2A	15203	45832;45833;45834	chr2:178607291;178607290;178607289	chr2:179472018;179472017;179472016
N2B	8706	26341;26342;26343	chr2:178607291;178607290;178607289	chr2:179472018;179472017;179472016
Novex-1	8831	26716;26717;26718	chr2:178607291;178607290;178607289	chr2:179472018;179472017;179472016
Novex-2	8898	26917;26918;26919	chr2:178607291;178607290;178607289	chr2:179472018;179472017;179472016
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-17
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.4578
• Predicted PPI site: I

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/I	rs2055111857	None	0.999	N	0.497	0.305	0.450539155747	gnomAD-4.0.0	1.59377E-06	None	None	None	None	I	None	0	0	None	0	2.78691E-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
L/A	0.953	likely_pathogenic	0.9614	pathogenic	-2.411	Highly Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
L/C	0.8989	likely_pathogenic	0.9077	pathogenic	-1.665	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
L/D	0.9991	likely_pathogenic	0.9993	pathogenic	-3.013	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
L/E	0.9947	likely_pathogenic	0.9965	pathogenic	-2.777	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
L/F	0.7534	likely_pathogenic	0.8232	pathogenic	-1.426	Destabilizing	1.0	D	0.713	prob.delet.	N	0.492399555	None	None	I
L/G	0.9909	likely_pathogenic	0.9918	pathogenic	-2.96	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
L/H	0.9912	likely_pathogenic	0.9935	pathogenic	-2.537	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
L/I	0.2405	likely_benign	0.3058	benign	-0.821	Destabilizing	0.999	D	0.497	neutral	N	0.479522313	None	None	I
L/K	0.9896	likely_pathogenic	0.9916	pathogenic	-2.043	Highly Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
L/M	0.3882	ambiguous	0.4889	ambiguous	-0.723	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
L/N	0.9945	likely_pathogenic	0.9957	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
L/P	0.981	likely_pathogenic	0.9773	pathogenic	-1.333	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
L/Q	0.984	likely_pathogenic	0.9888	pathogenic	-2.267	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
L/R	0.9834	likely_pathogenic	0.9859	pathogenic	-1.794	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
L/S	0.9937	likely_pathogenic	0.9949	pathogenic	-3.045	Highly Destabilizing	1.0	D	0.783	deleterious	N	0.504516329	None	None	I
L/T	0.9422	likely_pathogenic	0.9498	pathogenic	-2.663	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
L/V	0.3046	likely_benign	0.3388	benign	-1.333	Destabilizing	0.999	D	0.543	neutral	N	0.500701118	None	None	I
L/W	0.9731	likely_pathogenic	0.9812	pathogenic	-1.902	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
L/Y	0.9835	likely_pathogenic	0.9883	pathogenic	-1.561	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I

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.