TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20805	62638;62639;62640	chr2:178589312;178589311;178589310	chr2:179454039;179454038;179454037
N2AB	19164	57715;57716;57717	chr2:178589312;178589311;178589310	chr2:179454039;179454038;179454037
N2A	18237	54934;54935;54936	chr2:178589312;178589311;178589310	chr2:179454039;179454038;179454037
N2B	11740	35443;35444;35445	chr2:178589312;178589311;178589310	chr2:179454039;179454038;179454037
Novex-1	11865	35818;35819;35820	chr2:178589312;178589311;178589310	chr2:179454039;179454038;179454037
Novex-2	11932	36019;36020;36021	chr2:178589312;178589311;178589310	chr2:179454039;179454038;179454037
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-122
• Domain position: 37
• Structural Position: 50
• Q(SASA): 0.2118
• 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	rs1308910919	None	0.999	N	0.655	0.311	0.397838977388	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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	0.9569	likely_pathogenic	0.9693	pathogenic	-1.037	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
K/C	0.9533	likely_pathogenic	0.9657	pathogenic	-1.169	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
K/D	0.9931	likely_pathogenic	0.996	pathogenic	-0.816	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/E	0.924	likely_pathogenic	0.9376	pathogenic	-0.649	Destabilizing	0.999	D	0.633	neutral	D	0.536691779	None	None	N
K/F	0.9791	likely_pathogenic	0.9855	pathogenic	-0.681	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
K/G	0.9759	likely_pathogenic	0.9834	pathogenic	-1.453	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/H	0.782	likely_pathogenic	0.8225	pathogenic	-1.834	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/I	0.9166	likely_pathogenic	0.9407	pathogenic	0.077	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
K/L	0.8697	likely_pathogenic	0.8895	pathogenic	0.077	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/M	0.8394	likely_pathogenic	0.8735	pathogenic	0.015	Stabilizing	1.0	D	0.745	deleterious	D	0.525081984	None	None	N
K/N	0.9798	likely_pathogenic	0.9877	pathogenic	-1.111	Destabilizing	1.0	D	0.723	prob.delet.	N	0.518498619	None	None	N
K/P	0.9943	likely_pathogenic	0.9963	pathogenic	-0.266	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/Q	0.6802	likely_pathogenic	0.708	pathogenic	-1.11	Destabilizing	1.0	D	0.709	prob.delet.	N	0.50647075	None	None	N
K/R	0.1021	likely_benign	0.1004	benign	-0.997	Destabilizing	0.999	D	0.655	neutral	N	0.515683639	None	None	N
K/S	0.9787	likely_pathogenic	0.987	pathogenic	-1.792	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
K/T	0.9297	likely_pathogenic	0.9561	pathogenic	-1.391	Destabilizing	1.0	D	0.748	deleterious	N	0.513472189	None	None	N
K/V	0.8585	likely_pathogenic	0.892	pathogenic	-0.266	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/W	0.9623	likely_pathogenic	0.9705	pathogenic	-0.561	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/Y	0.946	likely_pathogenic	0.9595	pathogenic	-0.235	Destabilizing	1.0	D	0.812	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.