TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13868	41827;41828;41829	chr2:178635969;178635968;178635967	chr2:179500696;179500695;179500694
N2AB	12227	36904;36905;36906	chr2:178635969;178635968;178635967	chr2:179500696;179500695;179500694
N2A	11300	34123;34124;34125	chr2:178635969;178635968;178635967	chr2:179500696;179500695;179500694
N2B	4803	14632;14633;14634	chr2:178635969;178635968;178635967	chr2:179500696;179500695;179500694
Novex-1	4928	15007;15008;15009	chr2:178635969;178635968;178635967	chr2:179500696;179500695;179500694
Novex-2	4995	15208;15209;15210	chr2:178635969;178635968;178635967	chr2:179500696;179500695;179500694
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-88
• Domain position: 89
• Structural Position: 177
• Q(SASA): 0.2881
• 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/A	None	None	0.978	N	0.554	0.373	0.570859980718	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/L	None	None	0.9	N	0.492	0.246	0.480801007081	gnomAD-4.0.0	1.64207E-06	None	None	None	None	N	None	0	0	None	5.0221E-05	0	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	0.9191	likely_pathogenic	0.9282	pathogenic	-1.211	Destabilizing	0.978	D	0.554	neutral	N	0.461212684	None	None	N
V/C	0.9923	likely_pathogenic	0.9897	pathogenic	-0.861	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
V/D	0.9949	likely_pathogenic	0.9961	pathogenic	-0.965	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
V/E	0.9858	likely_pathogenic	0.9885	pathogenic	-1.018	Destabilizing	0.999	D	0.775	deleterious	N	0.463438974	None	None	N
V/F	0.9513	likely_pathogenic	0.9629	pathogenic	-1.026	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
V/G	0.9437	likely_pathogenic	0.9515	pathogenic	-1.462	Destabilizing	0.999	D	0.791	deleterious	N	0.463438974	None	None	N
V/H	0.998	likely_pathogenic	0.9982	pathogenic	-0.987	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/I	0.1705	likely_benign	0.162	benign	-0.652	Destabilizing	0.37	N	0.222	neutral	N	0.37509127	None	None	N
V/K	0.9919	likely_pathogenic	0.993	pathogenic	-1.069	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
V/L	0.905	likely_pathogenic	0.9063	pathogenic	-0.652	Destabilizing	0.9	D	0.492	neutral	N	0.417127998	None	None	N
V/M	0.8862	likely_pathogenic	0.894	pathogenic	-0.518	Destabilizing	0.998	D	0.648	neutral	None	None	None	None	N
V/N	0.9827	likely_pathogenic	0.9846	pathogenic	-0.786	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
V/P	0.9875	likely_pathogenic	0.985	pathogenic	-0.803	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
V/Q	0.9926	likely_pathogenic	0.9931	pathogenic	-1.018	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
V/R	0.9886	likely_pathogenic	0.9901	pathogenic	-0.502	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
V/S	0.9695	likely_pathogenic	0.9721	pathogenic	-1.244	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
V/T	0.8947	likely_pathogenic	0.8963	pathogenic	-1.197	Destabilizing	0.992	D	0.633	neutral	None	None	None	None	N
V/W	0.9991	likely_pathogenic	0.9992	pathogenic	-1.136	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
V/Y	0.9941	likely_pathogenic	0.9953	pathogenic	-0.873	Destabilizing	0.999	D	0.752	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.