TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29685	89278;89279;89280	chr2:178554058;178554057;178554056	chr2:179418785;179418784;179418783
N2AB	28044	84355;84356;84357	chr2:178554058;178554057;178554056	chr2:179418785;179418784;179418783
N2A	27117	81574;81575;81576	chr2:178554058;178554057;178554056	chr2:179418785;179418784;179418783
N2B	20620	62083;62084;62085	chr2:178554058;178554057;178554056	chr2:179418785;179418784;179418783
Novex-1	20745	62458;62459;62460	chr2:178554058;178554057;178554056	chr2:179418785;179418784;179418783
Novex-2	20812	62659;62660;62661	chr2:178554058;178554057;178554056	chr2:179418785;179418784;179418783
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-104
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.5291
• 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/R	rs773157007	-0.382	0.999	N	0.626	0.256	0.425970041486	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	1.15882E-04	None	0	0	None	0	None	0	0	0
K/R	rs773157007	-0.382	0.999	N	0.626	0.256	0.425970041486	gnomAD-4.0.0	6.36452E-06	None	None	None	None	N	None	0	9.14537E-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
K/A	0.6742	likely_pathogenic	0.8337	pathogenic	0.068	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/C	0.8809	likely_pathogenic	0.94	pathogenic	-0.452	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
K/D	0.7845	likely_pathogenic	0.8949	pathogenic	-0.199	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/E	0.4879	ambiguous	0.7351	pathogenic	-0.197	Destabilizing	0.999	D	0.679	prob.neutral	N	0.495546014	None	None	N
K/F	0.9566	likely_pathogenic	0.9843	pathogenic	-0.221	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
K/G	0.6274	likely_pathogenic	0.7833	pathogenic	-0.08	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/H	0.4786	ambiguous	0.6105	pathogenic	-0.163	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/I	0.8278	likely_pathogenic	0.9281	pathogenic	0.377	Stabilizing	1.0	D	0.831	deleterious	N	0.520596387	None	None	N
K/L	0.747	likely_pathogenic	0.8731	pathogenic	0.377	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/M	0.661	likely_pathogenic	0.8301	pathogenic	-0.096	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/N	0.7419	likely_pathogenic	0.8638	pathogenic	0.005	Stabilizing	1.0	D	0.782	deleterious	N	0.477454717	None	None	N
K/P	0.6265	likely_pathogenic	0.7709	pathogenic	0.298	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
K/Q	0.2613	likely_benign	0.4081	ambiguous	-0.103	Destabilizing	1.0	D	0.771	deleterious	N	0.466658297	None	None	N
K/R	0.0847	likely_benign	0.0951	benign	-0.079	Destabilizing	0.999	D	0.626	neutral	N	0.468975488	None	None	N
K/S	0.702	likely_pathogenic	0.8357	pathogenic	-0.353	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
K/T	0.4937	ambiguous	0.6826	pathogenic	-0.226	Destabilizing	1.0	D	0.774	deleterious	N	0.488443896	None	None	N
K/V	0.7694	likely_pathogenic	0.8917	pathogenic	0.298	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/W	0.8738	likely_pathogenic	0.9457	pathogenic	-0.335	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
K/Y	0.8599	likely_pathogenic	0.9354	pathogenic	0.022	Stabilizing	1.0	D	0.815	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.