TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7761	23506;23507;23508	chr2:178720481;178720480;178720479	chr2:179585208;179585207;179585206
N2AB	7444	22555;22556;22557	chr2:178720481;178720480;178720479	chr2:179585208;179585207;179585206
N2A	6517	19774;19775;19776	chr2:178720481;178720480;178720479	chr2:179585208;179585207;179585206
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: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-62
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0811
• 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	0.973	D	0.725	0.882	0.846497674913	gnomAD-4.0.0	1.68046E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.83751E-05	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
I/A	0.9735	likely_pathogenic	0.977	pathogenic	-3.093	Highly Destabilizing	0.97	D	0.712	prob.delet.	None	None	None	None	N
I/C	0.9619	likely_pathogenic	0.9634	pathogenic	-2.146	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
I/D	0.9992	likely_pathogenic	0.9991	pathogenic	-3.726	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/E	0.9983	likely_pathogenic	0.9982	pathogenic	-3.401	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
I/F	0.5105	ambiguous	0.5014	ambiguous	-1.826	Destabilizing	0.999	D	0.7	prob.neutral	D	0.560416452	None	None	N
I/G	0.9961	likely_pathogenic	0.9964	pathogenic	-3.687	Highly Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
I/H	0.9909	likely_pathogenic	0.99	pathogenic	-3.319	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
I/K	0.9943	likely_pathogenic	0.9936	pathogenic	-2.416	Highly Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
I/L	0.2807	likely_benign	0.2976	benign	-1.281	Destabilizing	0.049	N	0.379	neutral	D	0.571231264	None	None	N
I/M	0.4006	ambiguous	0.418	ambiguous	-1.448	Destabilizing	0.942	D	0.693	prob.neutral	D	0.599480834	None	None	N
I/N	0.9858	likely_pathogenic	0.984	pathogenic	-3.155	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.649183711	None	None	N
I/P	0.9981	likely_pathogenic	0.9983	pathogenic	-1.88	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
I/Q	0.9937	likely_pathogenic	0.9934	pathogenic	-2.786	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/R	0.9897	likely_pathogenic	0.989	pathogenic	-2.43	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
I/S	0.9806	likely_pathogenic	0.9809	pathogenic	-3.659	Highly Destabilizing	0.999	D	0.812	deleterious	D	0.649183711	None	None	N
I/T	0.9817	likely_pathogenic	0.9814	pathogenic	-3.178	Highly Destabilizing	0.973	D	0.725	prob.delet.	D	0.623241991	None	None	N
I/V	0.1462	likely_benign	0.1464	benign	-1.88	Destabilizing	0.006	N	0.273	neutral	D	0.537508423	None	None	N
I/W	0.9891	likely_pathogenic	0.9881	pathogenic	-2.2	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
I/Y	0.9427	likely_pathogenic	0.9419	pathogenic	-2.088	Highly Destabilizing	0.994	D	0.788	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.