TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21846	65761;65762;65763	chr2:178583646;178583645;178583644	chr2:179448373;179448372;179448371
N2AB	20205	60838;60839;60840	chr2:178583646;178583645;178583644	chr2:179448373;179448372;179448371
N2A	19278	58057;58058;58059	chr2:178583646;178583645;178583644	chr2:179448373;179448372;179448371
N2B	12781	38566;38567;38568	chr2:178583646;178583645;178583644	chr2:179448373;179448372;179448371
Novex-1	12906	38941;38942;38943	chr2:178583646;178583645;178583644	chr2:179448373;179448372;179448371
Novex-2	12973	39142;39143;39144	chr2:178583646;178583645;178583644	chr2:179448373;179448372;179448371
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-46
• Domain position: 90
• Structural Position: 121
• Q(SASA): 0.0799
• 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
S/P	None	None	1.0	D	0.859	0.704	0.667980572847	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
S/A	0.4758	ambiguous	0.4491	ambiguous	-0.824	Destabilizing	0.997	D	0.831	deleterious	N	0.491473817	None	None	N
S/C	0.5239	ambiguous	0.4646	ambiguous	-0.805	Destabilizing	1.0	D	0.867	deleterious	D	0.551915875	None	None	N
S/D	0.9925	likely_pathogenic	0.9888	pathogenic	-1.544	Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
S/E	0.9932	likely_pathogenic	0.9922	pathogenic	-1.403	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
S/F	0.9948	likely_pathogenic	0.9947	pathogenic	-0.468	Destabilizing	1.0	D	0.902	deleterious	D	0.551915875	None	None	N
S/G	0.4829	ambiguous	0.3916	ambiguous	-1.19	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
S/H	0.9905	likely_pathogenic	0.9895	pathogenic	-1.538	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
S/I	0.9845	likely_pathogenic	0.9847	pathogenic	0.088	Stabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
S/K	0.9987	likely_pathogenic	0.9986	pathogenic	-0.918	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
S/L	0.9334	likely_pathogenic	0.9313	pathogenic	0.088	Stabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
S/M	0.971	likely_pathogenic	0.9648	pathogenic	0.034	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
S/N	0.9699	likely_pathogenic	0.9569	pathogenic	-1.367	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
S/P	0.9893	likely_pathogenic	0.9905	pathogenic	-0.181	Destabilizing	1.0	D	0.859	deleterious	D	0.551662385	None	None	N
S/Q	0.9894	likely_pathogenic	0.9893	pathogenic	-1.216	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
S/R	0.9953	likely_pathogenic	0.9954	pathogenic	-1.085	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
S/T	0.6482	likely_pathogenic	0.5817	pathogenic	-1.08	Destabilizing	0.999	D	0.875	deleterious	N	0.512412001	None	None	N
S/V	0.9579	likely_pathogenic	0.9529	pathogenic	-0.181	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
S/W	0.9928	likely_pathogenic	0.9938	pathogenic	-0.699	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
S/Y	0.9916	likely_pathogenic	0.9923	pathogenic	-0.337	Destabilizing	1.0	D	0.901	deleterious	D	0.551662385	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.