TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10100	30523;30524;30525	chr2:178702589;178702588;178702587	chr2:179567316;179567315;179567314
N2AB	9783	29572;29573;29574	chr2:178702589;178702588;178702587	chr2:179567316;179567315;179567314
N2A	8856	26791;26792;26793	chr2:178702589;178702588;178702587	chr2:179567316;179567315;179567314
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-86
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2831
• 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/K	rs748645732	-1.044	0.999	None	0.601	0.393	0.385249989106	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
E/K	rs748645732	-1.044	0.999	None	0.601	0.393	0.385249989106	gnomAD-4.0.0	1.59086E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85747E-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	0.791	likely_pathogenic	0.8087	pathogenic	-0.728	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
E/C	0.9904	likely_pathogenic	0.9922	pathogenic	-0.494	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/D	0.9185	likely_pathogenic	0.9319	pathogenic	-1.354	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	N
E/F	0.9947	likely_pathogenic	0.9956	pathogenic	-0.808	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
E/G	0.9416	likely_pathogenic	0.953	pathogenic	-1.064	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
E/H	0.9776	likely_pathogenic	0.981	pathogenic	-1.178	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/I	0.9329	likely_pathogenic	0.9366	pathogenic	0.175	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
E/K	0.8819	likely_pathogenic	0.8767	pathogenic	-0.845	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
E/L	0.973	likely_pathogenic	0.9785	pathogenic	0.175	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/M	0.9448	likely_pathogenic	0.95	pathogenic	0.713	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/N	0.9686	likely_pathogenic	0.9728	pathogenic	-1.114	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.9995	pathogenic	-0.105	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/Q	0.6324	likely_pathogenic	0.6455	pathogenic	-0.988	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
E/R	0.9221	likely_pathogenic	0.9195	pathogenic	-0.785	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/S	0.875	likely_pathogenic	0.8874	pathogenic	-1.489	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
E/T	0.8722	likely_pathogenic	0.879	pathogenic	-1.208	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/V	0.8243	likely_pathogenic	0.8387	pathogenic	-0.105	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/W	0.9983	likely_pathogenic	0.9988	pathogenic	-0.863	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/Y	0.9927	likely_pathogenic	0.9941	pathogenic	-0.631	Destabilizing	1.0	D	0.795	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.