TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4996	15211;15212;15213	chr2:178734938;178734937;178734936	chr2:179599665;179599664;179599663
N2AB	4679	14260;14261;14262	chr2:178734938;178734937;178734936	chr2:179599665;179599664;179599663
N2A	3752	11479;11480;11481	chr2:178734938;178734937;178734936	chr2:179599665;179599664;179599663
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: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-33
• Domain position: 16
• Structural Position: 24
• Q(SASA): 0.2976
• 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/D	None	None	1.0	D	0.864	0.715	0.62430428174	gnomAD-4.0.0	1.60299E-06	None	None	None	None	I	None	0	2.32992E-05	None	0	0	None	0	0	0	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	0.4281	ambiguous	0.4774	ambiguous	-0.5	Destabilizing	1.0	D	0.788	deleterious	D	0.737783881	None	None	I
G/C	0.6962	likely_pathogenic	0.739	pathogenic	-0.983	Destabilizing	1.0	D	0.831	deleterious	D	0.80765844	None	None	I
G/D	0.5289	ambiguous	0.5732	pathogenic	-0.871	Destabilizing	1.0	D	0.864	deleterious	D	0.666012736	None	None	I
G/E	0.4914	ambiguous	0.5376	ambiguous	-1.028	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/F	0.9029	likely_pathogenic	0.9226	pathogenic	-1.168	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/H	0.6907	likely_pathogenic	0.713	pathogenic	-0.773	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/I	0.9292	likely_pathogenic	0.9493	pathogenic	-0.576	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/K	0.6145	likely_pathogenic	0.6502	pathogenic	-1.056	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
G/L	0.8296	likely_pathogenic	0.8674	pathogenic	-0.576	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/M	0.8538	likely_pathogenic	0.8852	pathogenic	-0.516	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/N	0.547	ambiguous	0.5671	pathogenic	-0.72	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/P	0.9896	likely_pathogenic	0.993	pathogenic	-0.517	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/Q	0.5447	ambiguous	0.5797	pathogenic	-1.029	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
G/R	0.4686	ambiguous	0.5061	ambiguous	-0.558	Destabilizing	1.0	D	0.864	deleterious	D	0.752979017	None	None	I
G/S	0.2476	likely_benign	0.2654	benign	-0.856	Destabilizing	1.0	D	0.843	deleterious	D	0.643841198	None	None	I
G/T	0.5714	likely_pathogenic	0.6009	pathogenic	-0.948	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
G/V	0.8272	likely_pathogenic	0.8694	pathogenic	-0.517	Destabilizing	1.0	D	0.831	deleterious	D	0.752641877	None	None	I
G/W	0.7958	likely_pathogenic	0.8205	pathogenic	-1.32	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/Y	0.8347	likely_pathogenic	0.8704	pathogenic	-0.987	Destabilizing	1.0	D	0.839	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.