TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20981	63166;63167;63168	chr2:178588784;178588783;178588782	chr2:179453511;179453510;179453509
N2AB	19340	58243;58244;58245	chr2:178588784;178588783;178588782	chr2:179453511;179453510;179453509
N2A	18413	55462;55463;55464	chr2:178588784;178588783;178588782	chr2:179453511;179453510;179453509
N2B	11916	35971;35972;35973	chr2:178588784;178588783;178588782	chr2:179453511;179453510;179453509
Novex-1	12041	36346;36347;36348	chr2:178588784;178588783;178588782	chr2:179453511;179453510;179453509
Novex-2	12108	36547;36548;36549	chr2:178588784;178588783;178588782	chr2:179453511;179453510;179453509
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-40
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.2996
• 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
T/P	rs1412315320	None	1.0	N	0.793	0.548	0.518421792786	gnomAD-4.0.0	1.36876E-06	None	None	None	None	N	None	0	0	None	3.82995E-05	0	None	0	0	8.99588E-07	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
T/A	0.2672	likely_benign	0.2351	benign	-1.01	Destabilizing	0.999	D	0.512	neutral	N	0.501936056	None	None	N
T/C	0.7488	likely_pathogenic	0.6642	pathogenic	-1.012	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
T/D	0.8928	likely_pathogenic	0.8255	pathogenic	-1.722	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/E	0.7996	likely_pathogenic	0.6906	pathogenic	-1.587	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/F	0.5972	likely_pathogenic	0.493	ambiguous	-0.618	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
T/G	0.7624	likely_pathogenic	0.6964	pathogenic	-1.373	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/H	0.7368	likely_pathogenic	0.6387	pathogenic	-1.6	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
T/I	0.2778	likely_benign	0.2113	benign	-0.085	Destabilizing	1.0	D	0.783	deleterious	N	0.47390368	None	None	N
T/K	0.8308	likely_pathogenic	0.7461	pathogenic	-1.054	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
T/L	0.1936	likely_benign	0.1494	benign	-0.085	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
T/M	0.116	likely_benign	0.0989	benign	-0.115	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
T/N	0.4676	ambiguous	0.3763	ambiguous	-1.505	Destabilizing	1.0	D	0.689	prob.neutral	N	0.518540304	None	None	N
T/P	0.8785	likely_pathogenic	0.8768	pathogenic	-0.361	Destabilizing	1.0	D	0.793	deleterious	N	0.506188624	None	None	N
T/Q	0.6828	likely_pathogenic	0.6088	pathogenic	-1.415	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
T/R	0.7767	likely_pathogenic	0.6811	pathogenic	-1.073	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
T/S	0.4067	ambiguous	0.3283	benign	-1.614	Destabilizing	0.999	D	0.483	neutral	N	0.478731122	None	None	N
T/V	0.1934	likely_benign	0.1606	benign	-0.361	Destabilizing	0.999	D	0.532	neutral	None	None	None	None	N
T/W	0.8435	likely_pathogenic	0.7594	pathogenic	-0.771	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/Y	0.6746	likely_pathogenic	0.5425	ambiguous	-0.443	Destabilizing	1.0	D	0.819	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.