TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9992	30199;30200;30201	chr2:178704396;178704395;178704394	chr2:179569123;179569122;179569121
N2AB	9675	29248;29249;29250	chr2:178704396;178704395;178704394	chr2:179569123;179569122;179569121
N2A	8748	26467;26468;26469	chr2:178704396;178704395;178704394	chr2:179569123;179569122;179569121
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-85
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5121
• 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
E/D	None	None	0.046	None	0.16	0.046	0.0611884634855	gnomAD-4.0.0	3.18488E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72243E-06	0	0
E/K	None	None	0.969	None	0.429	0.277	0.19670166235	gnomAD-4.0.0	1.36908E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79978E-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
E/A	0.5699	likely_pathogenic	0.6238	pathogenic	-0.932	Destabilizing	0.939	D	0.455	neutral	None	None	None	None	N
E/C	0.9862	likely_pathogenic	0.987	pathogenic	-0.395	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
E/D	0.6227	likely_pathogenic	0.7094	pathogenic	-0.655	Destabilizing	0.046	N	0.16	neutral	None	None	None	None	N
E/F	0.9675	likely_pathogenic	0.9768	pathogenic	-0.566	Destabilizing	0.986	D	0.647	neutral	None	None	None	None	N
E/G	0.6025	likely_pathogenic	0.646	pathogenic	-1.202	Destabilizing	0.969	D	0.475	neutral	None	None	None	None	N
E/H	0.9144	likely_pathogenic	0.9362	pathogenic	-0.56	Destabilizing	0.999	D	0.41	neutral	None	None	None	None	N
E/I	0.7003	likely_pathogenic	0.7518	pathogenic	-0.219	Destabilizing	0.128	N	0.409	neutral	None	None	None	None	N
E/K	0.5549	ambiguous	0.6323	pathogenic	-0.26	Destabilizing	0.969	D	0.429	neutral	None	None	None	None	N
E/L	0.7608	likely_pathogenic	0.8158	pathogenic	-0.219	Destabilizing	0.91	D	0.52	neutral	None	None	None	None	N
E/M	0.82	likely_pathogenic	0.8564	pathogenic	0.105	Stabilizing	0.996	D	0.578	neutral	None	None	None	None	N
E/N	0.8211	likely_pathogenic	0.8686	pathogenic	-0.674	Destabilizing	0.986	D	0.429	neutral	None	None	None	None	N
E/P	0.9838	likely_pathogenic	0.9883	pathogenic	-0.437	Destabilizing	0.998	D	0.489	neutral	None	None	None	None	N
E/Q	0.4004	ambiguous	0.4573	ambiguous	-0.613	Destabilizing	0.991	D	0.458	neutral	None	None	None	None	N
E/R	0.7527	likely_pathogenic	0.802	pathogenic	0.028	Stabilizing	0.993	D	0.421	neutral	None	None	None	None	N
E/S	0.7307	likely_pathogenic	0.7767	pathogenic	-0.905	Destabilizing	0.953	D	0.41	neutral	None	None	None	None	N
E/T	0.7182	likely_pathogenic	0.7541	pathogenic	-0.684	Destabilizing	0.986	D	0.453	neutral	None	None	None	None	N
E/V	0.51	ambiguous	0.5648	pathogenic	-0.437	Destabilizing	0.885	D	0.461	neutral	None	None	None	None	N
E/W	0.99	likely_pathogenic	0.9925	pathogenic	-0.288	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
E/Y	0.9488	likely_pathogenic	0.9622	pathogenic	-0.315	Destabilizing	0.998	D	0.591	neutral	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.