TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9059	27400;27401;27402	chr2:178712850;178712849;178712848	chr2:179577577;179577576;179577575
N2AB	8742	26449;26450;26451	chr2:178712850;178712849;178712848	chr2:179577577;179577576;179577575
N2A	7815	23668;23669;23670	chr2:178712850;178712849;178712848	chr2:179577577;179577576;179577575
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: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-76
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2266
• 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
L/R	rs780110919	-0.907	0.971	D	0.771	0.697	0.858135505271	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/R	rs780110919	-0.907	0.971	D	0.771	0.697	0.858135505271	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
L/R	rs780110919	-0.907	0.971	D	0.771	0.697	0.858135505271	gnomAD-4.0.0	1.30136E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.77997E-05	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
L/A	0.5504	ambiguous	0.5772	pathogenic	-2.102	Highly Destabilizing	0.86	D	0.479	neutral	None	None	None	None	I
L/C	0.7856	likely_pathogenic	0.8128	pathogenic	-1.162	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	I
L/D	0.9545	likely_pathogenic	0.9665	pathogenic	-2.262	Highly Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	I
L/E	0.7972	likely_pathogenic	0.8388	pathogenic	-2.037	Highly Destabilizing	0.993	D	0.791	deleterious	None	None	None	None	I
L/F	0.2553	likely_benign	0.2655	benign	-1.242	Destabilizing	0.956	D	0.563	neutral	None	None	None	None	I
L/G	0.8867	likely_pathogenic	0.9028	pathogenic	-2.624	Highly Destabilizing	0.978	D	0.774	deleterious	None	None	None	None	I
L/H	0.6642	likely_pathogenic	0.7194	pathogenic	-2.044	Highly Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	I
L/I	0.0854	likely_benign	0.0813	benign	-0.607	Destabilizing	0.014	N	0.277	neutral	N	0.48253751	None	None	I
L/K	0.6992	likely_pathogenic	0.7626	pathogenic	-1.512	Destabilizing	0.978	D	0.739	prob.delet.	None	None	None	None	I
L/M	0.1531	likely_benign	0.1588	benign	-0.457	Destabilizing	0.559	D	0.406	neutral	None	None	None	None	I
L/N	0.862	likely_pathogenic	0.8899	pathogenic	-1.849	Destabilizing	0.993	D	0.797	deleterious	None	None	None	None	I
L/P	0.857	likely_pathogenic	0.8686	pathogenic	-1.085	Destabilizing	0.99	D	0.799	deleterious	D	0.525572867	None	None	I
L/Q	0.5478	ambiguous	0.6129	pathogenic	-1.708	Destabilizing	0.971	D	0.771	deleterious	D	0.533232643	None	None	I
L/R	0.5657	likely_pathogenic	0.6371	pathogenic	-1.295	Destabilizing	0.971	D	0.771	deleterious	D	0.542195865	None	None	I
L/S	0.8102	likely_pathogenic	0.8439	pathogenic	-2.517	Highly Destabilizing	0.978	D	0.714	prob.delet.	None	None	None	None	I
L/T	0.5578	ambiguous	0.6111	pathogenic	-2.146	Highly Destabilizing	0.956	D	0.629	neutral	None	None	None	None	I
L/V	0.1115	likely_benign	0.1094	benign	-1.085	Destabilizing	0.247	N	0.439	neutral	N	0.493030753	None	None	I
L/W	0.4514	ambiguous	0.5054	ambiguous	-1.631	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	I
L/Y	0.592	likely_pathogenic	0.651	pathogenic	-1.265	Destabilizing	0.978	D	0.707	prob.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.