TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9219	27880;27881;27882	chr2:178712175;178712174;178712173	chr2:179576902;179576901;179576900
N2AB	8902	26929;26930;26931	chr2:178712175;178712174;178712173	chr2:179576902;179576901;179576900
N2A	7975	24148;24149;24150	chr2:178712175;178712174;178712173	chr2:179576902;179576901;179576900
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-78
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.289
• 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/R	None	None	1.0	D	0.904	0.876	0.899920238737	gnomAD-4.0.0	1.59135E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85843E-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	0.4333	ambiguous	0.5946	pathogenic	-0.292	Destabilizing	1.0	D	0.794	deleterious	D	0.620343497	None	None	I
G/C	0.621	likely_pathogenic	0.7997	pathogenic	-0.899	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/D	0.5337	ambiguous	0.6858	pathogenic	-0.347	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	I
G/E	0.5504	ambiguous	0.7005	pathogenic	-0.505	Destabilizing	1.0	D	0.886	deleterious	D	0.591999768	None	None	I
G/F	0.8694	likely_pathogenic	0.928	pathogenic	-0.985	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
G/H	0.695	likely_pathogenic	0.8185	pathogenic	-0.516	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
G/I	0.8868	likely_pathogenic	0.9529	pathogenic	-0.41	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/K	0.636	likely_pathogenic	0.765	pathogenic	-0.69	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
G/L	0.8064	likely_pathogenic	0.8893	pathogenic	-0.41	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/M	0.8443	likely_pathogenic	0.9203	pathogenic	-0.428	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/N	0.5115	ambiguous	0.5969	pathogenic	-0.386	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
G/P	0.9872	likely_pathogenic	0.9941	pathogenic	-0.337	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
G/Q	0.5965	likely_pathogenic	0.7399	pathogenic	-0.664	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
G/R	0.4869	ambiguous	0.6608	pathogenic	-0.288	Destabilizing	1.0	D	0.904	deleterious	D	0.632385699	None	None	I
G/S	0.2494	likely_benign	0.363	ambiguous	-0.582	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
G/T	0.5352	ambiguous	0.6787	pathogenic	-0.664	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/V	0.7936	likely_pathogenic	0.9095	pathogenic	-0.337	Destabilizing	1.0	D	0.868	deleterious	D	0.632587503	None	None	I
G/W	0.7251	likely_pathogenic	0.8582	pathogenic	-1.126	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	I
G/Y	0.7924	likely_pathogenic	0.8857	pathogenic	-0.766	Destabilizing	1.0	D	0.876	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.