TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16332	49219;49220;49221	chr2:178614520;178614519;178614518	chr2:179479247;179479246;179479245
N2AB	14691	44296;44297;44298	chr2:178614520;178614519;178614518	chr2:179479247;179479246;179479245
N2A	13764	41515;41516;41517	chr2:178614520;178614519;178614518	chr2:179479247;179479246;179479245
N2B	7267	22024;22025;22026	chr2:178614520;178614519;178614518	chr2:179479247;179479246;179479245
Novex-1	7392	22399;22400;22401	chr2:178614520;178614519;178614518	chr2:179479247;179479246;179479245
Novex-2	7459	22600;22601;22602	chr2:178614520;178614519;178614518	chr2:179479247;179479246;179479245
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-110
• Domain position: 71
• Structural Position: 157
• Q(SASA): 0.3432
• 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
E/K	rs879092258	None	0.999	N	0.675	0.446	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs879092258	None	0.999	N	0.675	0.446	None	gnomAD-4.0.0	2.56733E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.79393E-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	0.8028	likely_pathogenic	0.8307	pathogenic	-0.78	Destabilizing	0.999	D	0.731	prob.delet.	D	0.534190228	None	None	I
E/C	0.9909	likely_pathogenic	0.9885	pathogenic	-0.33	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
E/D	0.8366	likely_pathogenic	0.8407	pathogenic	-1.071	Destabilizing	0.999	D	0.61	neutral	D	0.585257024	None	None	I
E/F	0.9949	likely_pathogenic	0.9957	pathogenic	-0.61	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
E/G	0.9129	likely_pathogenic	0.9203	pathogenic	-1.101	Destabilizing	1.0	D	0.805	deleterious	D	0.6662541	None	None	I
E/H	0.9418	likely_pathogenic	0.9463	pathogenic	-0.956	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
E/I	0.9527	likely_pathogenic	0.9658	pathogenic	0.077	Stabilizing	1.0	D	0.901	deleterious	None	None	None	None	I
E/K	0.8058	likely_pathogenic	0.8547	pathogenic	-0.464	Destabilizing	0.999	D	0.675	neutral	N	0.495801937	None	None	I
E/L	0.9691	likely_pathogenic	0.975	pathogenic	0.077	Stabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
E/M	0.9533	likely_pathogenic	0.9618	pathogenic	0.527	Stabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
E/N	0.9142	likely_pathogenic	0.9199	pathogenic	-0.79	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
E/P	0.9996	likely_pathogenic	0.9997	pathogenic	-0.187	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
E/Q	0.5429	ambiguous	0.5638	ambiguous	-0.705	Destabilizing	1.0	D	0.711	prob.delet.	N	0.50619126	None	None	I
E/R	0.8978	likely_pathogenic	0.9168	pathogenic	-0.355	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
E/S	0.7693	likely_pathogenic	0.785	pathogenic	-1.08	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
E/T	0.7238	likely_pathogenic	0.7545	pathogenic	-0.818	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
E/V	0.8594	likely_pathogenic	0.8913	pathogenic	-0.187	Destabilizing	1.0	D	0.872	deleterious	N	0.487810275	None	None	I
E/W	0.9981	likely_pathogenic	0.9981	pathogenic	-0.473	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
E/Y	0.9883	likely_pathogenic	0.9897	pathogenic	-0.377	Destabilizing	1.0	D	0.896	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.