TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35759	107500;107501;107502	chr2:178528376;178528375;178528374	chr2:179393103;179393102;179393101
N2AB	34118	102577;102578;102579	chr2:178528376;178528375;178528374	chr2:179393103;179393102;179393101
N2A	33191	99796;99797;99798	chr2:178528376;178528375;178528374	chr2:179393103;179393102;179393101
N2B	26694	80305;80306;80307	chr2:178528376;178528375;178528374	chr2:179393103;179393102;179393101
Novex-1	26819	80680;80681;80682	chr2:178528376;178528375;178528374	chr2:179393103;179393102;179393101
Novex-2	26886	80881;80882;80883	chr2:178528376;178528375;178528374	chr2:179393103;179393102;179393101
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-168
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0635
• 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/F	rs1307850517	-1.551	1.0	D	0.802	0.712	0.715330771395	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
L/F	rs1307850517	-1.551	1.0	D	0.802	0.712	0.715330771395	gnomAD-4.0.0	1.59099E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	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	0.881	likely_pathogenic	0.8924	pathogenic	-2.006	Highly Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
L/C	0.891	likely_pathogenic	0.9036	pathogenic	-1.388	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9994	pathogenic	-2.674	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/E	0.9949	likely_pathogenic	0.9948	pathogenic	-2.346	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/F	0.4062	ambiguous	0.4084	ambiguous	-1.231	Destabilizing	1.0	D	0.802	deleterious	D	0.524990209	None	None	N
L/G	0.9828	likely_pathogenic	0.9841	pathogenic	-2.608	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/H	0.9822	likely_pathogenic	0.9817	pathogenic	-2.62	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.566353734	None	None	N
L/I	0.2127	likely_benign	0.2265	benign	-0.201	Destabilizing	0.999	D	0.639	neutral	D	0.523153331	None	None	N
L/K	0.9884	likely_pathogenic	0.9869	pathogenic	-1.447	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/M	0.2479	likely_benign	0.2488	benign	-0.506	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/N	0.9966	likely_pathogenic	0.9964	pathogenic	-2.183	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/P	0.9967	likely_pathogenic	0.9971	pathogenic	-0.793	Destabilizing	1.0	D	0.911	deleterious	D	0.57771004	None	None	N
L/Q	0.9712	likely_pathogenic	0.9702	pathogenic	-1.733	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/R	0.9696	likely_pathogenic	0.9701	pathogenic	-1.845	Destabilizing	1.0	D	0.904	deleterious	D	0.57771004	None	None	N
L/S	0.9854	likely_pathogenic	0.9865	pathogenic	-2.697	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/T	0.9403	likely_pathogenic	0.947	pathogenic	-2.187	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/V	0.2439	likely_benign	0.2665	benign	-0.793	Destabilizing	0.999	D	0.651	neutral	D	0.535118747	None	None	N
L/W	0.9009	likely_pathogenic	0.8997	pathogenic	-1.607	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/Y	0.9486	likely_pathogenic	0.9482	pathogenic	-1.332	Destabilizing	1.0	D	0.859	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.