TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2209	6850;6851;6852	chr2:178775086;178775085;178775084	chr2:179639813;179639812;179639811
N2AB	2209	6850;6851;6852	chr2:178775086;178775085;178775084	chr2:179639813;179639812;179639811
N2A	2209	6850;6851;6852	chr2:178775086;178775085;178775084	chr2:179639813;179639812;179639811
N2B	2163	6712;6713;6714	chr2:178775086;178775085;178775084	chr2:179639813;179639812;179639811
Novex-1	2163	6712;6713;6714	chr2:178775086;178775085;178775084	chr2:179639813;179639812;179639811
Novex-2	2163	6712;6713;6714	chr2:178775086;178775085;178775084	chr2:179639813;179639812;179639811
Novex-3	2209	6850;6851;6852	chr2:178775086;178775085;178775084	chr2:179639813;179639812;179639811

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-11
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1831
• 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
K/Q	rs1260981476	None	1.0	N	0.69	0.324	0.12205267543	gnomAD-4.0.0	1.59075E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85678E-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
K/A	0.8446	likely_pathogenic	0.8602	pathogenic	-1.198	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
K/C	0.8602	likely_pathogenic	0.8646	pathogenic	-1.246	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
K/D	0.9758	likely_pathogenic	0.9801	pathogenic	-1.367	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
K/E	0.6855	likely_pathogenic	0.7154	pathogenic	-1.11	Destabilizing	0.999	D	0.589	neutral	D	0.548409638	None	None	N
K/F	0.9494	likely_pathogenic	0.9535	pathogenic	-0.512	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
K/G	0.9169	likely_pathogenic	0.9274	pathogenic	-1.695	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
K/H	0.5477	ambiguous	0.5638	ambiguous	-1.929	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
K/I	0.7123	likely_pathogenic	0.726	pathogenic	0.183	Stabilizing	1.0	D	0.857	deleterious	N	0.473965052	None	None	N
K/L	0.728	likely_pathogenic	0.7525	pathogenic	0.183	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
K/M	0.5824	likely_pathogenic	0.608	pathogenic	0.002	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/N	0.9101	likely_pathogenic	0.9181	pathogenic	-1.546	Destabilizing	1.0	D	0.712	prob.delet.	D	0.548409638	None	None	N
K/P	0.9937	likely_pathogenic	0.9951	pathogenic	-0.251	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
K/Q	0.3511	ambiguous	0.3633	ambiguous	-1.282	Destabilizing	1.0	D	0.69	prob.neutral	N	0.474992712	None	None	N
K/R	0.0928	likely_benign	0.0954	benign	-1.142	Destabilizing	0.999	D	0.604	neutral	N	0.338184048	None	None	N
K/S	0.8974	likely_pathogenic	0.9064	pathogenic	-2.135	Highly Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
K/T	0.7402	likely_pathogenic	0.7599	pathogenic	-1.613	Destabilizing	1.0	D	0.787	deleterious	D	0.548215863	None	None	N
K/V	0.6776	likely_pathogenic	0.6972	pathogenic	-0.251	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
K/W	0.9422	likely_pathogenic	0.9461	pathogenic	-0.516	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
K/Y	0.8943	likely_pathogenic	0.9001	pathogenic	-0.188	Destabilizing	1.0	D	0.833	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.