TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6464	19615;19616;19617	chr2:178728536;178728535;178728534	chr2:179593263;179593262;179593261
N2AB	6147	18664;18665;18666	chr2:178728536;178728535;178728534	chr2:179593263;179593262;179593261
N2A	5220	15883;15884;15885	chr2:178728536;178728535;178728534	chr2:179593263;179593262;179593261
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-48
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2061
• 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	0.998	D	0.767	0.741	0.632648996995	gnomAD-4.0.0	1.59491E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86494E-06	0	0
G/R	rs755082868	None	1.0	D	0.763	0.691	0.621853638575	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
G/R	rs755082868	None	1.0	D	0.763	0.691	0.621853638575	gnomAD-4.0.0	6.57505E-06	None	None	None	None	I	None	0	6.5591E-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	0.7813	likely_pathogenic	0.7826	pathogenic	-0.327	Destabilizing	0.962	D	0.505	neutral	D	0.631017737	None	None	I
G/C	0.9311	likely_pathogenic	0.9269	pathogenic	-0.897	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
G/D	0.9211	likely_pathogenic	0.924	pathogenic	-0.707	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	I
G/E	0.9608	likely_pathogenic	0.9565	pathogenic	-0.881	Destabilizing	0.998	D	0.767	deleterious	D	0.538272299	None	None	I
G/F	0.9853	likely_pathogenic	0.9839	pathogenic	-1.124	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
G/H	0.9744	likely_pathogenic	0.9726	pathogenic	-0.515	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/I	0.9802	likely_pathogenic	0.9759	pathogenic	-0.529	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
G/K	0.9849	likely_pathogenic	0.9825	pathogenic	-0.761	Destabilizing	0.998	D	0.764	deleterious	None	None	None	None	I
G/L	0.9755	likely_pathogenic	0.9732	pathogenic	-0.529	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
G/M	0.9906	likely_pathogenic	0.9902	pathogenic	-0.482	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
G/N	0.9556	likely_pathogenic	0.9604	pathogenic	-0.45	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	I
G/P	0.9977	likely_pathogenic	0.9974	pathogenic	-0.431	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
G/Q	0.9568	likely_pathogenic	0.9552	pathogenic	-0.776	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	I
G/R	0.9441	likely_pathogenic	0.9379	pathogenic	-0.274	Destabilizing	1.0	D	0.763	deleterious	D	0.631219541	None	None	I
G/S	0.6232	likely_pathogenic	0.6431	pathogenic	-0.564	Destabilizing	0.862	D	0.28	neutral	None	None	None	None	I
G/T	0.9349	likely_pathogenic	0.9336	pathogenic	-0.675	Destabilizing	0.996	D	0.773	deleterious	None	None	None	None	I
G/V	0.9632	likely_pathogenic	0.9553	pathogenic	-0.431	Destabilizing	0.999	D	0.759	deleterious	D	0.631824954	None	None	I
G/W	0.9761	likely_pathogenic	0.9719	pathogenic	-1.24	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
G/Y	0.9783	likely_pathogenic	0.9758	pathogenic	-0.902	Destabilizing	1.0	D	0.79	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.