TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7195	21808;21809;21810	chr2:178723517;178723516;178723515	chr2:179588244;179588243;179588242
N2AB	6878	20857;20858;20859	chr2:178723517;178723516;178723515	chr2:179588244;179588243;179588242
N2A	5951	18076;18077;18078	chr2:178723517;178723516;178723515	chr2:179588244;179588243;179588242
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-56
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.1809
• 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/G	rs2078794868	None	0.993	D	0.703	0.454	0.582232187747	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.9305E-04	None	0	0	0	0	0
E/G	rs2078794868	None	0.993	D	0.703	0.454	0.582232187747	gnomAD-4.0.0	6.57134E-06	None	None	None	None	N	None	0	0	None	0	1.9305E-04	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
E/A	0.3611	ambiguous	0.3724	ambiguous	-0.929	Destabilizing	0.977	D	0.549	neutral	N	0.493606048	None	None	N
E/C	0.9449	likely_pathogenic	0.9464	pathogenic	-0.536	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/D	0.5052	ambiguous	0.5583	ambiguous	-1.389	Destabilizing	0.977	D	0.495	neutral	N	0.510508989	None	None	N
E/F	0.9061	likely_pathogenic	0.9054	pathogenic	-0.277	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/G	0.514	ambiguous	0.5516	ambiguous	-1.379	Destabilizing	0.993	D	0.703	prob.neutral	D	0.525650729	None	None	N
E/H	0.6843	likely_pathogenic	0.6836	pathogenic	-0.619	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/I	0.5831	likely_pathogenic	0.6067	pathogenic	0.336	Stabilizing	0.998	D	0.811	deleterious	None	None	None	None	N
E/K	0.393	ambiguous	0.4025	ambiguous	-1.09	Destabilizing	0.117	N	0.391	neutral	N	0.482908079	None	None	N
E/L	0.6582	likely_pathogenic	0.6737	pathogenic	0.336	Stabilizing	0.995	D	0.77	deleterious	None	None	None	None	N
E/M	0.6612	likely_pathogenic	0.661	pathogenic	0.987	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/N	0.6616	likely_pathogenic	0.6964	pathogenic	-1.549	Destabilizing	0.995	D	0.659	neutral	None	None	None	None	N
E/P	0.9884	likely_pathogenic	0.9905	pathogenic	-0.066	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
E/Q	0.1962	likely_benign	0.1989	benign	-1.287	Destabilizing	0.977	D	0.584	neutral	D	0.535598417	None	None	N
E/R	0.4995	ambiguous	0.5066	ambiguous	-0.879	Destabilizing	0.99	D	0.649	neutral	None	None	None	None	N
E/S	0.4731	ambiguous	0.4962	ambiguous	-2.064	Highly Destabilizing	0.983	D	0.525	neutral	None	None	None	None	N
E/T	0.4762	ambiguous	0.4961	ambiguous	-1.67	Destabilizing	0.995	D	0.713	prob.delet.	None	None	None	None	N
E/V	0.365	ambiguous	0.3794	ambiguous	-0.066	Destabilizing	0.997	D	0.751	deleterious	N	0.495135874	None	None	N
E/W	0.9667	likely_pathogenic	0.9652	pathogenic	-0.16	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/Y	0.8453	likely_pathogenic	0.8469	pathogenic	-0.049	Destabilizing	0.999	D	0.783	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.