TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20196	60811;60812;60813	chr2:178591139;178591138;178591137	chr2:179455866;179455865;179455864
N2AB	18555	55888;55889;55890	chr2:178591139;178591138;178591137	chr2:179455866;179455865;179455864
N2A	17628	53107;53108;53109	chr2:178591139;178591138;178591137	chr2:179455866;179455865;179455864
N2B	11131	33616;33617;33618	chr2:178591139;178591138;178591137	chr2:179455866;179455865;179455864
Novex-1	11256	33991;33992;33993	chr2:178591139;178591138;178591137	chr2:179455866;179455865;179455864
Novex-2	11323	34192;34193;34194	chr2:178591139;178591138;178591137	chr2:179455866;179455865;179455864
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-34
• Domain position: 26
• Structural Position: 27
• Q(SASA): 0.1857
• 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
P/H	None	None	1.0	D	0.874	0.492	0.594452868026	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
P/A	0.8221	likely_pathogenic	0.8886	pathogenic	-1.957	Destabilizing	1.0	D	0.834	deleterious	D	0.526364156	None	None	N
P/C	0.9762	likely_pathogenic	0.9838	pathogenic	-1.351	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
P/D	0.9985	likely_pathogenic	0.9993	pathogenic	-2.545	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/E	0.9946	likely_pathogenic	0.9978	pathogenic	-2.491	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/F	0.9991	likely_pathogenic	0.9995	pathogenic	-1.484	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/G	0.9868	likely_pathogenic	0.9925	pathogenic	-2.345	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/H	0.9942	likely_pathogenic	0.9974	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.874	deleterious	D	0.542519855	None	None	N
P/I	0.9867	likely_pathogenic	0.9932	pathogenic	-0.938	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/K	0.9975	likely_pathogenic	0.9989	pathogenic	-1.784	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/L	0.9531	likely_pathogenic	0.9751	pathogenic	-0.938	Destabilizing	1.0	D	0.889	deleterious	D	0.540745428	None	None	N
P/M	0.9908	likely_pathogenic	0.9955	pathogenic	-0.641	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/N	0.9979	likely_pathogenic	0.9989	pathogenic	-1.68	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/Q	0.9901	likely_pathogenic	0.9957	pathogenic	-1.784	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/R	0.9913	likely_pathogenic	0.9959	pathogenic	-1.306	Destabilizing	1.0	D	0.89	deleterious	D	0.527124625	None	None	N
P/S	0.9579	likely_pathogenic	0.9805	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.847	deleterious	N	0.495004265	None	None	N
P/T	0.9539	likely_pathogenic	0.9808	pathogenic	-1.974	Destabilizing	1.0	D	0.845	deleterious	D	0.523655131	None	None	N
P/V	0.9536	likely_pathogenic	0.9736	pathogenic	-1.247	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9998	pathogenic	-1.866	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/Y	0.9991	likely_pathogenic	0.9996	pathogenic	-1.579	Destabilizing	1.0	D	0.891	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.