TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6101	18526;18527;18528	chr2:178730099;178730098;178730097	chr2:179594826;179594825;179594824
N2AB	5784	17575;17576;17577	chr2:178730099;178730098;178730097	chr2:179594826;179594825;179594824
N2A	4857	14794;14795;14796	chr2:178730099;178730098;178730097	chr2:179594826;179594825;179594824
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-44
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.6365
• 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/L	None	None	0.997	D	0.763	0.688	0.739959095934	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
V/A	0.7805	likely_pathogenic	0.8264	pathogenic	-1.906	Destabilizing	0.999	D	0.763	deleterious	D	0.633144708	None	None	N
V/C	0.9492	likely_pathogenic	0.9584	pathogenic	-1.509	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/D	0.9852	likely_pathogenic	0.9915	pathogenic	-2.3	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/E	0.9505	likely_pathogenic	0.9693	pathogenic	-2.203	Highly Destabilizing	1.0	D	0.807	deleterious	D	0.633750121	None	None	N
V/F	0.6782	likely_pathogenic	0.791	pathogenic	-1.287	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
V/G	0.8594	likely_pathogenic	0.896	pathogenic	-2.317	Highly Destabilizing	1.0	D	0.774	deleterious	D	0.61773076	None	None	N
V/H	0.9841	likely_pathogenic	0.991	pathogenic	-1.891	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/I	0.0825	likely_benign	0.0885	benign	-0.813	Destabilizing	0.997	D	0.725	prob.delet.	N	0.515625821	None	None	N
V/K	0.9668	likely_pathogenic	0.9796	pathogenic	-1.488	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/L	0.4942	ambiguous	0.5868	pathogenic	-0.813	Destabilizing	0.997	D	0.763	deleterious	D	0.631126666	None	None	N
V/M	0.555	ambiguous	0.6674	pathogenic	-0.803	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/N	0.9568	likely_pathogenic	0.9713	pathogenic	-1.533	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/P	0.9435	likely_pathogenic	0.9538	pathogenic	-1.147	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/Q	0.9357	likely_pathogenic	0.9592	pathogenic	-1.595	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/R	0.9353	likely_pathogenic	0.9585	pathogenic	-1.105	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/S	0.8696	likely_pathogenic	0.9057	pathogenic	-2.11	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
V/T	0.8022	likely_pathogenic	0.8408	pathogenic	-1.897	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
V/W	0.9869	likely_pathogenic	0.9939	pathogenic	-1.631	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/Y	0.9626	likely_pathogenic	0.9793	pathogenic	-1.31	Destabilizing	1.0	D	0.855	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.