TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15275	46048;46049;46050	chr2:178620787;178620786;178620785	chr2:179485514;179485513;179485512
N2AB	13634	41125;41126;41127	chr2:178620787;178620786;178620785	chr2:179485514;179485513;179485512
N2A	12707	38344;38345;38346	chr2:178620787;178620786;178620785	chr2:179485514;179485513;179485512
N2B	6210	18853;18854;18855	chr2:178620787;178620786;178620785	chr2:179485514;179485513;179485512
Novex-1	6335	19228;19229;19230	chr2:178620787;178620786;178620785	chr2:179485514;179485513;179485512
Novex-2	6402	19429;19430;19431	chr2:178620787;178620786;178620785	chr2:179485514;179485513;179485512
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-104
• Domain position: 68
• Structural Position: 152
• Q(SASA): 0.1192
• 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
A/V	rs760059046	-0.348	0.84	D	0.727	0.318	0.235038932564	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	8.94E-06	0
A/V	rs760059046	-0.348	0.84	D	0.727	0.318	0.235038932564	gnomAD-4.0.0	4.78004E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.58811E-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
A/C	0.7256	likely_pathogenic	0.7214	pathogenic	-1.054	Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
A/D	0.4697	ambiguous	0.4456	ambiguous	-1.707	Destabilizing	0.018	N	0.664	neutral	N	0.438783624	None	None	N
A/E	0.6132	likely_pathogenic	0.5804	pathogenic	-1.705	Destabilizing	0.633	D	0.789	deleterious	None	None	None	None	N
A/F	0.7898	likely_pathogenic	0.7796	pathogenic	-1.179	Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	N
A/G	0.0977	likely_benign	0.1024	benign	-1.402	Destabilizing	0.008	N	0.453	neutral	N	0.363828752	None	None	N
A/H	0.8527	likely_pathogenic	0.8448	pathogenic	-1.601	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
A/I	0.8499	likely_pathogenic	0.8518	pathogenic	-0.426	Destabilizing	0.961	D	0.809	deleterious	None	None	None	None	N
A/K	0.85	likely_pathogenic	0.8201	pathogenic	-1.352	Destabilizing	0.923	D	0.808	deleterious	None	None	None	None	N
A/L	0.6604	likely_pathogenic	0.6522	pathogenic	-0.426	Destabilizing	0.875	D	0.8	deleterious	None	None	None	None	N
A/M	0.6615	likely_pathogenic	0.6522	pathogenic	-0.315	Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	N
A/N	0.5568	ambiguous	0.5514	ambiguous	-1.166	Destabilizing	0.858	D	0.818	deleterious	None	None	None	None	N
A/P	0.9745	likely_pathogenic	0.9765	pathogenic	-0.611	Destabilizing	0.949	D	0.809	deleterious	D	0.573764265	None	None	N
A/Q	0.7053	likely_pathogenic	0.6703	pathogenic	-1.305	Destabilizing	0.961	D	0.805	deleterious	None	None	None	None	N
A/R	0.7574	likely_pathogenic	0.71	pathogenic	-1.003	Destabilizing	0.961	D	0.81	deleterious	None	None	None	None	N
A/S	0.1059	likely_benign	0.1121	benign	-1.512	Destabilizing	0.092	N	0.478	neutral	N	0.489321916	None	None	N
A/T	0.2426	likely_benign	0.2363	benign	-1.415	Destabilizing	0.722	D	0.709	prob.delet.	D	0.532004545	None	None	N
A/V	0.5412	ambiguous	0.5419	ambiguous	-0.611	Destabilizing	0.84	D	0.727	prob.delet.	D	0.532004545	None	None	N
A/W	0.9643	likely_pathogenic	0.9602	pathogenic	-1.593	Destabilizing	0.996	D	0.825	deleterious	None	None	None	None	N
A/Y	0.8687	likely_pathogenic	0.8543	pathogenic	-1.169	Destabilizing	0.987	D	0.845	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.