TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17066	51421;51422;51423	chr2:178610330;178610329;178610328	chr2:179475057;179475056;179475055
N2AB	15425	46498;46499;46500	chr2:178610330;178610329;178610328	chr2:179475057;179475056;179475055
N2A	14498	43717;43718;43719	chr2:178610330;178610329;178610328	chr2:179475057;179475056;179475055
N2B	8001	24226;24227;24228	chr2:178610330;178610329;178610328	chr2:179475057;179475056;179475055
Novex-1	8126	24601;24602;24603	chr2:178610330;178610329;178610328	chr2:179475057;179475056;179475055
Novex-2	8193	24802;24803;24804	chr2:178610330;178610329;178610328	chr2:179475057;179475056;179475055
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-12
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1125
• 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
L/S	None	None	0.984	D	0.815	0.646	0.828760804546	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
L/A	0.9388	likely_pathogenic	0.942	pathogenic	-2.593	Highly Destabilizing	0.702	D	0.739	prob.delet.	None	None	None	None	N
L/C	0.9174	likely_pathogenic	0.9276	pathogenic	-2.06	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9996	pathogenic	-2.978	Highly Destabilizing	0.996	D	0.896	deleterious	None	None	None	None	N
L/E	0.997	likely_pathogenic	0.9972	pathogenic	-2.651	Highly Destabilizing	0.988	D	0.885	deleterious	None	None	None	None	N
L/F	0.758	likely_pathogenic	0.7675	pathogenic	-1.558	Destabilizing	0.968	D	0.708	prob.delet.	D	0.668578198	None	None	N
L/G	0.9924	likely_pathogenic	0.9928	pathogenic	-3.237	Highly Destabilizing	0.988	D	0.873	deleterious	None	None	None	None	N
L/H	0.9952	likely_pathogenic	0.9957	pathogenic	-2.94	Highly Destabilizing	0.999	D	0.902	deleterious	None	None	None	None	N
L/I	0.0916	likely_benign	0.1035	benign	-0.676	Destabilizing	0.103	N	0.306	neutral	N	0.494490341	None	None	N
L/K	0.9965	likely_pathogenic	0.9971	pathogenic	-1.931	Destabilizing	0.988	D	0.834	deleterious	None	None	None	None	N
L/M	0.2948	likely_benign	0.3279	benign	-0.902	Destabilizing	0.988	D	0.673	neutral	None	None	None	None	N
L/N	0.9966	likely_pathogenic	0.9969	pathogenic	-2.568	Highly Destabilizing	0.996	D	0.9	deleterious	None	None	None	None	N
L/P	0.9967	likely_pathogenic	0.997	pathogenic	-1.302	Destabilizing	0.996	D	0.895	deleterious	None	None	None	None	N
L/Q	0.9923	likely_pathogenic	0.9931	pathogenic	-2.208	Highly Destabilizing	0.996	D	0.876	deleterious	None	None	None	None	N
L/R	0.9945	likely_pathogenic	0.9948	pathogenic	-2.031	Highly Destabilizing	0.988	D	0.866	deleterious	None	None	None	None	N
L/S	0.9954	likely_pathogenic	0.9961	pathogenic	-3.271	Highly Destabilizing	0.984	D	0.815	deleterious	D	0.746855905	None	None	N
L/T	0.9653	likely_pathogenic	0.97	pathogenic	-2.76	Highly Destabilizing	0.919	D	0.75	deleterious	None	None	None	None	N
L/V	0.1105	likely_benign	0.1219	benign	-1.302	Destabilizing	0.011	N	0.305	neutral	N	0.480864345	None	None	N
L/W	0.9876	likely_pathogenic	0.9885	pathogenic	-1.941	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
L/Y	0.9791	likely_pathogenic	0.9818	pathogenic	-1.675	Destabilizing	0.988	D	0.777	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.