TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24241	72946;72947;72948	chr2:178573411;178573410;178573409	chr2:179438138;179438137;179438136
N2AB	22600	68023;68024;68025	chr2:178573411;178573410;178573409	chr2:179438138;179438137;179438136
N2A	21673	65242;65243;65244	chr2:178573411;178573410;178573409	chr2:179438138;179438137;179438136
N2B	15176	45751;45752;45753	chr2:178573411;178573410;178573409	chr2:179438138;179438137;179438136
Novex-1	15301	46126;46127;46128	chr2:178573411;178573410;178573409	chr2:179438138;179438137;179438136
Novex-2	15368	46327;46328;46329	chr2:178573411;178573410;178573409	chr2:179438138;179438137;179438136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-64
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0978
• 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
V/I	rs756997225	-0.232	0.997	N	0.53	0.254	0.649348744143	gnomAD-2.1.1	5.68E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	5.77E-05	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	0.7417	likely_pathogenic	0.7657	pathogenic	-2.185	Highly Destabilizing	0.999	D	0.601	neutral	N	0.506860187	None	None	N
V/C	0.9343	likely_pathogenic	0.9304	pathogenic	-1.567	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/D	0.9977	likely_pathogenic	0.9972	pathogenic	-3.32	Highly Destabilizing	1.0	D	0.916	deleterious	D	0.534372191	None	None	N
V/E	0.9931	likely_pathogenic	0.992	pathogenic	-3.004	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/F	0.7514	likely_pathogenic	0.7262	pathogenic	-1.273	Destabilizing	1.0	D	0.797	deleterious	N	0.500668442	None	None	N
V/G	0.9209	likely_pathogenic	0.9145	pathogenic	-2.778	Highly Destabilizing	1.0	D	0.912	deleterious	D	0.534372191	None	None	N
V/H	0.997	likely_pathogenic	0.9962	pathogenic	-2.828	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/I	0.0729	likely_benign	0.0713	benign	-0.461	Destabilizing	0.997	D	0.53	neutral	N	0.464684389	None	None	N
V/K	0.995	likely_pathogenic	0.9938	pathogenic	-1.846	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/L	0.1851	likely_benign	0.2033	benign	-0.461	Destabilizing	0.997	D	0.621	neutral	N	0.401432626	None	None	N
V/M	0.4585	ambiguous	0.4518	ambiguous	-0.679	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
V/N	0.9905	likely_pathogenic	0.9885	pathogenic	-2.54	Highly Destabilizing	1.0	D	0.933	deleterious	None	None	None	None	N
V/P	0.9907	likely_pathogenic	0.9901	pathogenic	-1.018	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/Q	0.9905	likely_pathogenic	0.9887	pathogenic	-2.173	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
V/R	0.9904	likely_pathogenic	0.9881	pathogenic	-1.978	Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	N
V/S	0.954	likely_pathogenic	0.951	pathogenic	-2.987	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/T	0.8764	likely_pathogenic	0.8739	pathogenic	-2.519	Highly Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
V/W	0.9964	likely_pathogenic	0.9953	pathogenic	-1.924	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/Y	0.9847	likely_pathogenic	0.9804	pathogenic	-1.551	Destabilizing	1.0	D	0.803	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.