TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2982	9169;9170;9171	chr2:178768892;178768891;178768890	chr2:179633619;179633618;179633617
N2AB	2982	9169;9170;9171	chr2:178768892;178768891;178768890	chr2:179633619;179633618;179633617
N2A	2982	9169;9170;9171	chr2:178768892;178768891;178768890	chr2:179633619;179633618;179633617
N2B	2936	9031;9032;9033	chr2:178768892;178768891;178768890	chr2:179633619;179633618;179633617
Novex-1	2936	9031;9032;9033	chr2:178768892;178768891;178768890	chr2:179633619;179633618;179633617
Novex-2	2936	9031;9032;9033	chr2:178768892;178768891;178768890	chr2:179633619;179633618;179633617
Novex-3	2982	9169;9170;9171	chr2:178768892;178768891;178768890	chr2:179633619;179633618;179633617

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-20
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.2509
• 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	rs2090998936	None	1.0	D	0.652	0.545	0.446111551642	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.9584	likely_pathogenic	0.9423	pathogenic	-0.883	Destabilizing	0.999	D	0.587	neutral	N	0.475171451	None	None	N
E/C	0.9993	likely_pathogenic	0.9988	pathogenic	-0.518	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/D	0.9885	likely_pathogenic	0.9811	pathogenic	-1.234	Destabilizing	0.999	D	0.444	neutral	D	0.530584517	None	None	N
E/F	0.9995	likely_pathogenic	0.9992	pathogenic	-0.303	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
E/G	0.9586	likely_pathogenic	0.9422	pathogenic	-1.274	Destabilizing	1.0	D	0.652	neutral	D	0.624645129	None	None	N
E/H	0.9991	likely_pathogenic	0.9987	pathogenic	-0.661	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/I	0.9931	likely_pathogenic	0.9893	pathogenic	0.191	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/K	0.9794	likely_pathogenic	0.9719	pathogenic	-0.741	Destabilizing	0.999	D	0.566	neutral	N	0.491816609	None	None	N
E/L	0.9961	likely_pathogenic	0.9942	pathogenic	0.191	Stabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/M	0.9931	likely_pathogenic	0.9906	pathogenic	0.677	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/N	0.996	likely_pathogenic	0.9941	pathogenic	-1.227	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/P	0.996	likely_pathogenic	0.9949	pathogenic	-0.145	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/Q	0.9541	likely_pathogenic	0.9383	pathogenic	-1.064	Destabilizing	1.0	D	0.627	neutral	D	0.622762584	None	None	N
E/R	0.9901	likely_pathogenic	0.9833	pathogenic	-0.495	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/S	0.9916	likely_pathogenic	0.9876	pathogenic	-1.572	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
E/T	0.992	likely_pathogenic	0.9891	pathogenic	-1.243	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
E/V	0.9816	likely_pathogenic	0.9729	pathogenic	-0.145	Destabilizing	1.0	D	0.701	prob.neutral	N	0.499238031	None	None	N
E/W	0.9998	likely_pathogenic	0.9997	pathogenic	-0.071	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/Y	0.9991	likely_pathogenic	0.9985	pathogenic	-0.055	Destabilizing	1.0	D	0.723	prob.delet.	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.