TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19691	59296;59297;59298	chr2:178593048;178593047;178593046	chr2:179457775;179457774;179457773
N2AB	18050	54373;54374;54375	chr2:178593048;178593047;178593046	chr2:179457775;179457774;179457773
N2A	17123	51592;51593;51594	chr2:178593048;178593047;178593046	chr2:179457775;179457774;179457773
N2B	10626	32101;32102;32103	chr2:178593048;178593047;178593046	chr2:179457775;179457774;179457773
Novex-1	10751	32476;32477;32478	chr2:178593048;178593047;178593046	chr2:179457775;179457774;179457773
Novex-2	10818	32677;32678;32679	chr2:178593048;178593047;178593046	chr2:179457775;179457774;179457773
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-31
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4739
• 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
D/E	None	None	0.963	N	0.431	0.275	0.307016933798	gnomAD-4.0.0	1.36873E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79918E-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
D/A	0.6899	likely_pathogenic	0.5745	pathogenic	-0.34	Destabilizing	0.865	D	0.623	neutral	N	0.472178479	None	None	N
D/C	0.9521	likely_pathogenic	0.9239	pathogenic	0.135	Stabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
D/E	0.6317	likely_pathogenic	0.5258	ambiguous	-0.437	Destabilizing	0.963	D	0.431	neutral	N	0.501682552	None	None	N
D/F	0.9346	likely_pathogenic	0.8956	pathogenic	-0.42	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
D/G	0.6543	likely_pathogenic	0.5512	ambiguous	-0.552	Destabilizing	0.039	N	0.342	neutral	N	0.482244564	None	None	N
D/H	0.8191	likely_pathogenic	0.7325	pathogenic	-0.544	Destabilizing	0.999	D	0.701	prob.neutral	N	0.505668418	None	None	N
D/I	0.9207	likely_pathogenic	0.8482	pathogenic	0.173	Stabilizing	0.992	D	0.759	deleterious	None	None	None	None	N
D/K	0.9173	likely_pathogenic	0.8684	pathogenic	0.209	Stabilizing	0.983	D	0.776	deleterious	None	None	None	None	N
D/L	0.8849	likely_pathogenic	0.8201	pathogenic	0.173	Stabilizing	0.992	D	0.753	deleterious	None	None	None	None	N
D/M	0.9637	likely_pathogenic	0.9334	pathogenic	0.487	Stabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
D/N	0.3182	likely_benign	0.2372	benign	-0.008	Destabilizing	0.978	D	0.688	prob.neutral	N	0.464758966	None	None	N
D/P	0.993	likely_pathogenic	0.9864	pathogenic	0.025	Stabilizing	0.997	D	0.773	deleterious	None	None	None	None	N
D/Q	0.8728	likely_pathogenic	0.814	pathogenic	0.011	Stabilizing	0.997	D	0.725	prob.delet.	None	None	None	None	N
D/R	0.8981	likely_pathogenic	0.8517	pathogenic	0.237	Stabilizing	0.992	D	0.729	prob.delet.	None	None	None	None	N
D/S	0.4649	ambiguous	0.3593	ambiguous	-0.131	Destabilizing	0.944	D	0.61	neutral	None	None	None	None	N
D/T	0.7891	likely_pathogenic	0.6836	pathogenic	0.03	Stabilizing	0.992	D	0.774	deleterious	None	None	None	None	N
D/V	0.8111	likely_pathogenic	0.6943	pathogenic	0.025	Stabilizing	0.989	D	0.761	deleterious	N	0.495842595	None	None	N
D/W	0.9872	likely_pathogenic	0.9806	pathogenic	-0.329	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
D/Y	0.7204	likely_pathogenic	0.6139	pathogenic	-0.195	Destabilizing	0.999	D	0.731	prob.delet.	N	0.500895478	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.