TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9928	30007;30008;30009	chr2:178704690;178704689;178704688	chr2:179569417;179569416;179569415
N2AB	9611	29056;29057;29058	chr2:178704690;178704689;178704688	chr2:179569417;179569416;179569415
N2A	8684	26275;26276;26277	chr2:178704690;178704689;178704688	chr2:179569417;179569416;179569415
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-84
• Domain position: 29
• Structural Position: 42
• Q(SASA): 0.5285
• 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
P/S	None	None	1.0	None	0.753	0.618	0.549504238362	gnomAD-4.0.0	6.8528E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00165E-07	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	0.7831	likely_pathogenic	0.7512	pathogenic	-0.535	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
P/C	0.9964	likely_pathogenic	0.9954	pathogenic	-0.783	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
P/D	0.9591	likely_pathogenic	0.957	pathogenic	-0.497	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
P/E	0.9058	likely_pathogenic	0.8964	pathogenic	-0.573	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/F	0.9982	likely_pathogenic	0.9978	pathogenic	-0.626	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
P/G	0.9625	likely_pathogenic	0.9577	pathogenic	-0.68	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
P/H	0.9351	likely_pathogenic	0.919	pathogenic	-0.103	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
P/I	0.9917	likely_pathogenic	0.9908	pathogenic	-0.28	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/K	0.9205	likely_pathogenic	0.9132	pathogenic	-0.584	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
P/L	0.9119	likely_pathogenic	0.8853	pathogenic	-0.28	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
P/M	0.989	likely_pathogenic	0.9871	pathogenic	-0.567	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
P/N	0.9689	likely_pathogenic	0.9674	pathogenic	-0.468	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/Q	0.8679	likely_pathogenic	0.851	pathogenic	-0.645	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
P/R	0.8541	likely_pathogenic	0.8279	pathogenic	-0.083	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
P/S	0.8533	likely_pathogenic	0.8327	pathogenic	-0.799	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
P/T	0.8824	likely_pathogenic	0.8681	pathogenic	-0.772	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/V	0.9788	likely_pathogenic	0.976	pathogenic	-0.333	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
P/W	0.9982	likely_pathogenic	0.9971	pathogenic	-0.727	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
P/Y	0.9965	likely_pathogenic	0.9951	pathogenic	-0.443	Destabilizing	1.0	D	0.751	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.