TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8676	26251;26252;26253	chr2:178715160;178715159;178715158	chr2:179579887;179579886;179579885
N2AB	8359	25300;25301;25302	chr2:178715160;178715159;178715158	chr2:179579887;179579886;179579885
N2A	7432	22519;22520;22521	chr2:178715160;178715159;178715158	chr2:179579887;179579886;179579885
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-72
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1277
• 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
W/R	None	None	1.0	D	0.888	0.928	0.94125591744	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
W/A	0.9929	likely_pathogenic	0.9907	pathogenic	-2.8	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
W/C	0.9941	likely_pathogenic	0.9937	pathogenic	-1.342	Destabilizing	1.0	D	0.819	deleterious	D	0.712352038	None	None	N
W/D	0.9998	likely_pathogenic	0.9996	pathogenic	-3.113	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
W/E	0.9995	likely_pathogenic	0.9993	pathogenic	-2.986	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
W/F	0.5834	likely_pathogenic	0.559	ambiguous	-1.677	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
W/G	0.9825	likely_pathogenic	0.9799	pathogenic	-3.045	Highly Destabilizing	1.0	D	0.84	deleterious	D	0.712150234	None	None	N
W/H	0.9961	likely_pathogenic	0.9948	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
W/I	0.9591	likely_pathogenic	0.948	pathogenic	-1.871	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
W/K	0.9997	likely_pathogenic	0.9995	pathogenic	-2.161	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
W/L	0.9137	likely_pathogenic	0.8991	pathogenic	-1.871	Destabilizing	1.0	D	0.84	deleterious	D	0.679879347	None	None	N
W/M	0.9845	likely_pathogenic	0.9831	pathogenic	-1.326	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
W/N	0.9993	likely_pathogenic	0.999	pathogenic	-2.885	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
W/P	0.999	likely_pathogenic	0.9986	pathogenic	-2.209	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
W/Q	0.9995	likely_pathogenic	0.9992	pathogenic	-2.689	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
W/R	0.9989	likely_pathogenic	0.9984	pathogenic	-2.013	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.712352038	None	None	N
W/S	0.9921	likely_pathogenic	0.9896	pathogenic	-3.022	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.712352038	None	None	N
W/T	0.9943	likely_pathogenic	0.9919	pathogenic	-2.822	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
W/V	0.9606	likely_pathogenic	0.9504	pathogenic	-2.209	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
W/Y	0.9036	likely_pathogenic	0.8895	pathogenic	-1.49	Destabilizing	1.0	D	0.794	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.