TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6444	19555;19556;19557	chr2:178728596;178728595;178728594	chr2:179593323;179593322;179593321
N2AB	6127	18604;18605;18606	chr2:178728596;178728595;178728594	chr2:179593323;179593322;179593321
N2A	5200	15823;15824;15825	chr2:178728596;178728595;178728594	chr2:179593323;179593322;179593321
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-48
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0732
• 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
I/M	None	None	0.968	D	0.697	0.763	0.672494282746	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

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
I/A	0.9485	likely_pathogenic	0.9403	pathogenic	-2.61	Highly Destabilizing	0.959	D	0.704	prob.neutral	None	None	None	None	N
I/C	0.9405	likely_pathogenic	0.9335	pathogenic	-1.622	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
I/D	0.9951	likely_pathogenic	0.9939	pathogenic	-3.199	Highly Destabilizing	0.996	D	0.908	deleterious	None	None	None	None	N
I/E	0.9868	likely_pathogenic	0.9839	pathogenic	-2.892	Highly Destabilizing	0.996	D	0.905	deleterious	None	None	None	None	N
I/F	0.2913	likely_benign	0.2854	benign	-1.452	Destabilizing	0.059	N	0.351	neutral	D	0.540682456	None	None	N
I/G	0.9859	likely_pathogenic	0.9838	pathogenic	-3.173	Highly Destabilizing	0.988	D	0.887	deleterious	None	None	None	None	N
I/H	0.9531	likely_pathogenic	0.9505	pathogenic	-2.923	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
I/K	0.946	likely_pathogenic	0.9437	pathogenic	-1.759	Destabilizing	0.996	D	0.903	deleterious	None	None	None	None	N
I/L	0.18	likely_benign	0.2184	benign	-0.906	Destabilizing	0.011	N	0.27	neutral	D	0.568877105	None	None	N
I/M	0.2138	likely_benign	0.2238	benign	-1.146	Destabilizing	0.968	D	0.697	prob.neutral	D	0.582764979	None	None	N
I/N	0.9266	likely_pathogenic	0.9107	pathogenic	-2.417	Highly Destabilizing	0.995	D	0.901	deleterious	D	0.648487217	None	None	N
I/P	0.9906	likely_pathogenic	0.991	pathogenic	-1.467	Destabilizing	0.996	D	0.908	deleterious	None	None	None	None	N
I/Q	0.9566	likely_pathogenic	0.9528	pathogenic	-2.069	Highly Destabilizing	0.996	D	0.915	deleterious	None	None	None	None	N
I/R	0.9267	likely_pathogenic	0.9245	pathogenic	-1.878	Destabilizing	0.996	D	0.905	deleterious	None	None	None	None	N
I/S	0.9421	likely_pathogenic	0.9284	pathogenic	-2.891	Highly Destabilizing	0.984	D	0.839	deleterious	D	0.648487217	None	None	N
I/T	0.9657	likely_pathogenic	0.9591	pathogenic	-2.437	Highly Destabilizing	0.946	D	0.789	deleterious	D	0.594685739	None	None	N
I/V	0.2443	likely_benign	0.2197	benign	-1.467	Destabilizing	0.437	N	0.437	neutral	D	0.558721655	None	None	N
I/W	0.9264	likely_pathogenic	0.929	pathogenic	-1.855	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
I/Y	0.7896	likely_pathogenic	0.7967	pathogenic	-1.68	Destabilizing	0.952	D	0.797	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.