TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6498	19717;19718;19719	chr2:178728332;178728331;178728330	chr2:179593059;179593058;179593057
N2AB	6181	18766;18767;18768	chr2:178728332;178728331;178728330	chr2:179593059;179593058;179593057
N2A	5254	15985;15986;15987	chr2:178728332;178728331;178728330	chr2:179593059;179593058;179593057
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-49
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1185
• 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
I/T	None	None	0.896	N	0.659	0.265	0.57436675	gnomAD-4.0.0	4.79111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72711E-06	0	3.03343E-05

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
I/A	0.3382	likely_benign	0.4727	ambiguous	-2.273	Highly Destabilizing	0.702	D	0.617	neutral	None	None	None	None	N
I/C	0.6331	likely_pathogenic	0.7309	pathogenic	-1.508	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
I/D	0.8282	likely_pathogenic	0.9186	pathogenic	-1.83	Destabilizing	0.996	D	0.819	deleterious	None	None	None	None	N
I/E	0.7782	likely_pathogenic	0.8774	pathogenic	-1.742	Destabilizing	0.988	D	0.804	deleterious	None	None	None	None	N
I/F	0.1548	likely_benign	0.1978	benign	-1.505	Destabilizing	0.984	D	0.685	prob.neutral	N	0.4992686	None	None	N
I/G	0.6889	likely_pathogenic	0.8098	pathogenic	-2.697	Highly Destabilizing	0.988	D	0.793	deleterious	None	None	None	None	N
I/H	0.6585	likely_pathogenic	0.7889	pathogenic	-1.791	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
I/K	0.6661	likely_pathogenic	0.7918	pathogenic	-1.695	Destabilizing	0.988	D	0.805	deleterious	None	None	None	None	N
I/L	0.1105	likely_benign	0.1455	benign	-1.119	Destabilizing	0.437	N	0.402	neutral	N	0.4643638	None	None	N
I/M	0.1178	likely_benign	0.16	benign	-0.905	Destabilizing	0.984	D	0.645	neutral	N	0.46017557	None	None	N
I/N	0.4505	ambiguous	0.6067	pathogenic	-1.634	Destabilizing	0.995	D	0.813	deleterious	N	0.4901431	None	None	N
I/P	0.8692	likely_pathogenic	0.9351	pathogenic	-1.477	Destabilizing	0.996	D	0.819	deleterious	None	None	None	None	N
I/Q	0.6408	likely_pathogenic	0.7795	pathogenic	-1.714	Destabilizing	0.996	D	0.808	deleterious	None	None	None	None	N
I/R	0.5418	ambiguous	0.6937	pathogenic	-1.109	Destabilizing	0.988	D	0.812	deleterious	None	None	None	None	N
I/S	0.3673	ambiguous	0.5131	ambiguous	-2.332	Highly Destabilizing	0.984	D	0.762	deleterious	N	0.46339157	None	None	N
I/T	0.2756	likely_benign	0.3921	ambiguous	-2.106	Highly Destabilizing	0.896	D	0.659	neutral	N	0.47052458	None	None	N
I/V	0.0662	likely_benign	0.0737	benign	-1.477	Destabilizing	0.004	N	0.169	neutral	N	0.36972007	None	None	N
I/W	0.8148	likely_pathogenic	0.8874	pathogenic	-1.612	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
I/Y	0.5654	likely_pathogenic	0.6714	pathogenic	-1.42	Destabilizing	0.996	D	0.789	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.