TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6176	18751;18752;18753	chr2:178729727;178729726;178729725	chr2:179594454;179594453;179594452
N2AB	5859	17800;17801;17802	chr2:178729727;178729726;178729725	chr2:179594454;179594453;179594452
N2A	4932	15019;15020;15021	chr2:178729727;178729726;178729725	chr2:179594454;179594453;179594452
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-45
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.1247
• 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
Y/H	None	None	1.0	D	0.809	0.796	0.858506001042	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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
Y/A	0.8831	likely_pathogenic	0.8957	pathogenic	-1.401	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/C	0.5107	ambiguous	0.5234	ambiguous	-0.739	Destabilizing	1.0	D	0.89	deleterious	D	0.689782115	None	None	N
Y/D	0.9897	likely_pathogenic	0.9903	pathogenic	-2.298	Highly Destabilizing	1.0	D	0.906	deleterious	D	0.689983919	None	None	N
Y/E	0.9933	likely_pathogenic	0.9933	pathogenic	-2.074	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
Y/F	0.0908	likely_benign	0.0939	benign	-0.453	Destabilizing	0.999	D	0.693	prob.neutral	D	0.586075955	None	None	N
Y/G	0.9428	likely_pathogenic	0.9449	pathogenic	-1.795	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
Y/H	0.8739	likely_pathogenic	0.8763	pathogenic	-1.908	Destabilizing	1.0	D	0.809	deleterious	D	0.68958031	None	None	N
Y/I	0.5413	ambiguous	0.5579	ambiguous	-0.104	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/K	0.9911	likely_pathogenic	0.9911	pathogenic	-1.193	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/L	0.4915	ambiguous	0.459	ambiguous	-0.104	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
Y/M	0.7915	likely_pathogenic	0.7837	pathogenic	-0.307	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/N	0.9368	likely_pathogenic	0.9365	pathogenic	-2.041	Highly Destabilizing	1.0	D	0.904	deleterious	D	0.689782115	None	None	N
Y/P	0.9915	likely_pathogenic	0.9925	pathogenic	-0.548	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
Y/Q	0.9859	likely_pathogenic	0.9863	pathogenic	-1.529	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/R	0.966	likely_pathogenic	0.9669	pathogenic	-1.83	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
Y/S	0.8824	likely_pathogenic	0.8897	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.906	deleterious	D	0.689782115	None	None	N
Y/T	0.9321	likely_pathogenic	0.941	pathogenic	-1.789	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/V	0.4092	ambiguous	0.421	ambiguous	-0.548	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/W	0.5738	likely_pathogenic	0.6008	pathogenic	-0.032	Destabilizing	1.0	D	0.8	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.