TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21785	65578;65579;65580	chr2:178583829;178583828;178583827	chr2:179448556;179448555;179448554
N2AB	20144	60655;60656;60657	chr2:178583829;178583828;178583827	chr2:179448556;179448555;179448554
N2A	19217	57874;57875;57876	chr2:178583829;178583828;178583827	chr2:179448556;179448555;179448554
N2B	12720	38383;38384;38385	chr2:178583829;178583828;178583827	chr2:179448556;179448555;179448554
Novex-1	12845	38758;38759;38760	chr2:178583829;178583828;178583827	chr2:179448556;179448555;179448554
Novex-2	12912	38959;38960;38961	chr2:178583829;178583828;178583827	chr2:179448556;179448555;179448554
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-46
• Domain position: 29
• Structural Position: 31
• Q(SASA): 0.3495
• Predicted PPI site: I

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
G/E	None	None	1.0	N	0.866	0.642	0.614800550379	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.8632	likely_pathogenic	0.8356	pathogenic	-0.15	Destabilizing	1.0	D	0.744	deleterious	N	0.507932916	None	None	I
G/C	0.9536	likely_pathogenic	0.9438	pathogenic	-0.814	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/D	0.9896	likely_pathogenic	0.9867	pathogenic	-0.464	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/E	0.9929	likely_pathogenic	0.9914	pathogenic	-0.632	Destabilizing	1.0	D	0.866	deleterious	N	0.513755813	None	None	I
G/F	0.9953	likely_pathogenic	0.9942	pathogenic	-0.951	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/H	0.995	likely_pathogenic	0.9934	pathogenic	-0.403	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
G/I	0.9929	likely_pathogenic	0.9908	pathogenic	-0.356	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/K	0.9945	likely_pathogenic	0.9926	pathogenic	-0.635	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
G/L	0.9919	likely_pathogenic	0.9899	pathogenic	-0.356	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/M	0.9951	likely_pathogenic	0.9938	pathogenic	-0.435	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
G/N	0.9891	likely_pathogenic	0.9837	pathogenic	-0.28	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/P	0.9987	likely_pathogenic	0.9979	pathogenic	-0.257	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/Q	0.9904	likely_pathogenic	0.9873	pathogenic	-0.562	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/R	0.9763	likely_pathogenic	0.9718	pathogenic	-0.229	Destabilizing	1.0	D	0.853	deleterious	N	0.484802232	None	None	I
G/S	0.8376	likely_pathogenic	0.7994	pathogenic	-0.411	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/T	0.9761	likely_pathogenic	0.9683	pathogenic	-0.51	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/V	0.9862	likely_pathogenic	0.9826	pathogenic	-0.257	Destabilizing	1.0	D	0.837	deleterious	N	0.511655899	None	None	I
G/W	0.9859	likely_pathogenic	0.9861	pathogenic	-1.097	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/Y	0.9935	likely_pathogenic	0.9909	pathogenic	-0.742	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I

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.