TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7072	21439;21440;21441	chr2:178724045;178724044;178724043	chr2:179588772;179588771;179588770
N2AB	6755	20488;20489;20490	chr2:178724045;178724044;178724043	chr2:179588772;179588771;179588770
N2A	5828	17707;17708;17709	chr2:178724045;178724044;178724043	chr2:179588772;179588771;179588770
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-55
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7344
• 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
P/H	rs1370301283	0.234	1.0	D	0.649	0.496	0.747146340571	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	9.97E-05	0	None	0	None	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
P/A	0.2923	likely_benign	0.3008	benign	-0.293	Destabilizing	1.0	D	0.647	neutral	N	0.496212941	None	None	I
P/C	0.8561	likely_pathogenic	0.8746	pathogenic	-0.699	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
P/D	0.6756	likely_pathogenic	0.6936	pathogenic	0.044	Stabilizing	1.0	D	0.656	neutral	None	None	None	None	I
P/E	0.5724	likely_pathogenic	0.6094	pathogenic	-0.068	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
P/F	0.8513	likely_pathogenic	0.8569	pathogenic	-0.579	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
P/G	0.5899	likely_pathogenic	0.6203	pathogenic	-0.385	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
P/H	0.5167	ambiguous	0.55	ambiguous	-0.019	Destabilizing	1.0	D	0.649	neutral	D	0.534195878	None	None	I
P/I	0.7374	likely_pathogenic	0.743	pathogenic	-0.2	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
P/K	0.6499	likely_pathogenic	0.6942	pathogenic	-0.261	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
P/L	0.4222	ambiguous	0.4184	ambiguous	-0.2	Destabilizing	1.0	D	0.699	prob.neutral	N	0.501341503	None	None	I
P/M	0.715	likely_pathogenic	0.7226	pathogenic	-0.377	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
P/N	0.5981	likely_pathogenic	0.6189	pathogenic	-0.066	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
P/Q	0.4431	ambiguous	0.4748	ambiguous	-0.258	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
P/R	0.4538	ambiguous	0.4971	ambiguous	0.147	Stabilizing	1.0	D	0.683	prob.neutral	N	0.494758137	None	None	I
P/S	0.3631	ambiguous	0.3824	ambiguous	-0.438	Destabilizing	1.0	D	0.678	prob.neutral	N	0.487414303	None	None	I
P/T	0.3199	likely_benign	0.3351	benign	-0.448	Destabilizing	1.0	D	0.671	neutral	N	0.488704523	None	None	I
P/V	0.5731	likely_pathogenic	0.5801	pathogenic	-0.199	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
P/W	0.9242	likely_pathogenic	0.931	pathogenic	-0.658	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
P/Y	0.8047	likely_pathogenic	0.821	pathogenic	-0.356	Destabilizing	1.0	D	0.659	neutral	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.