TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3961	12106;12107;12108	chr2:178741352;178741351;178741350	chr2:179606079;179606078;179606077
N2AB	3644	11155;11156;11157	chr2:178741352;178741351;178741350	chr2:179606079;179606078;179606077
N2A	None	None	chr2:None	chr2:None
N2B	3598	11017;11018;11019	chr2:178741352;178741351;178741350	chr2:179606079;179606078;179606077
Novex-1	3723	11392;11393;11394	chr2:178741352;178741351;178741350	chr2:179606079;179606078;179606077
Novex-2	3790	11593;11594;11595	chr2:178741352;178741351;178741350	chr2:179606079;179606078;179606077
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-28
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1353
• 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
V/M	rs1017307763	None	0.982	D	0.746	0.428	None	gnomAD-4.0.0	2.05252E-06	None	None	None	None	I	None	5.97514E-05	0	None	0	2.5194E-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
V/A	0.3493	ambiguous	0.2997	benign	-2.117	Highly Destabilizing	0.17	N	0.348	neutral	D	0.52935795	None	None	I
V/C	0.9167	likely_pathogenic	0.9057	pathogenic	-1.544	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
V/D	0.983	likely_pathogenic	0.9731	pathogenic	-2.665	Highly Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	I
V/E	0.9509	likely_pathogenic	0.9279	pathogenic	-2.406	Highly Destabilizing	0.991	D	0.821	deleterious	D	0.760087314	None	None	I
V/F	0.6015	likely_pathogenic	0.5534	ambiguous	-1.144	Destabilizing	0.986	D	0.797	deleterious	None	None	None	None	I
V/G	0.768	likely_pathogenic	0.6912	pathogenic	-2.695	Highly Destabilizing	0.964	D	0.805	deleterious	D	0.700686014	None	None	I
V/H	0.9845	likely_pathogenic	0.9781	pathogenic	-2.436	Highly Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	I
V/I	0.1059	likely_benign	0.1071	benign	-0.48	Destabilizing	0.06	N	0.264	neutral	None	None	None	None	I
V/K	0.9711	likely_pathogenic	0.9578	pathogenic	-1.688	Destabilizing	0.986	D	0.821	deleterious	None	None	None	None	I
V/L	0.464	ambiguous	0.4131	ambiguous	-0.48	Destabilizing	0.76	D	0.614	neutral	D	0.624881722	None	None	I
V/M	0.3783	ambiguous	0.3381	benign	-0.577	Destabilizing	0.982	D	0.746	deleterious	D	0.760791673	None	None	I
V/N	0.9547	likely_pathogenic	0.9355	pathogenic	-2.091	Highly Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	I
V/P	0.9697	likely_pathogenic	0.9635	pathogenic	-1.001	Destabilizing	0.993	D	0.819	deleterious	None	None	None	None	I
V/Q	0.9573	likely_pathogenic	0.9397	pathogenic	-1.863	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	I
V/R	0.9481	likely_pathogenic	0.9275	pathogenic	-1.62	Destabilizing	0.993	D	0.835	deleterious	None	None	None	None	I
V/S	0.7566	likely_pathogenic	0.6976	pathogenic	-2.73	Highly Destabilizing	0.973	D	0.791	deleterious	None	None	None	None	I
V/T	0.5234	ambiguous	0.469	ambiguous	-2.321	Highly Destabilizing	0.953	D	0.681	prob.neutral	None	None	None	None	I
V/W	0.9881	likely_pathogenic	0.9837	pathogenic	-1.691	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	I
V/Y	0.9557	likely_pathogenic	0.9419	pathogenic	-1.307	Destabilizing	0.998	D	0.783	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.