TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31290	94093;94094;94095	chr2:178547758;178547757;178547756	chr2:179412485;179412484;179412483
N2AB	29649	89170;89171;89172	chr2:178547758;178547757;178547756	chr2:179412485;179412484;179412483
N2A	28722	86389;86390;86391	chr2:178547758;178547757;178547756	chr2:179412485;179412484;179412483
N2B	22225	66898;66899;66900	chr2:178547758;178547757;178547756	chr2:179412485;179412484;179412483
Novex-1	22350	67273;67274;67275	chr2:178547758;178547757;178547756	chr2:179412485;179412484;179412483
Novex-2	22417	67474;67475;67476	chr2:178547758;178547757;178547756	chr2:179412485;179412484;179412483
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-151
• Domain position: 73
• Structural Position: 158
• Q(SASA): 0.1501
• 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
L/P	rs755965938	-1.79	1.0	N	0.783	0.716	0.890960720082	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.87E-06	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
L/A	0.4656	ambiguous	0.5307	ambiguous	-2.549	Highly Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
L/C	0.7247	likely_pathogenic	0.7574	pathogenic	-2.004	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
L/D	0.999	likely_pathogenic	0.9993	pathogenic	-2.827	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
L/E	0.9909	likely_pathogenic	0.9937	pathogenic	-2.595	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
L/F	0.8166	likely_pathogenic	0.8639	pathogenic	-1.503	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
L/G	0.9365	likely_pathogenic	0.9505	pathogenic	-3.104	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
L/H	0.99	likely_pathogenic	0.9941	pathogenic	-2.614	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
L/I	0.2089	likely_benign	0.2501	benign	-0.947	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	I
L/K	0.9914	likely_pathogenic	0.9942	pathogenic	-1.946	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
L/M	0.2562	likely_benign	0.3344	benign	-1.06	Destabilizing	1.0	D	0.763	deleterious	N	0.488846335	None	None	I
L/N	0.9933	likely_pathogenic	0.9954	pathogenic	-2.294	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
L/P	0.9934	likely_pathogenic	0.9958	pathogenic	-1.462	Destabilizing	1.0	D	0.783	deleterious	N	0.50720408	None	None	I
L/Q	0.964	likely_pathogenic	0.9784	pathogenic	-2.132	Highly Destabilizing	1.0	D	0.787	deleterious	N	0.50720408	None	None	I
L/R	0.9739	likely_pathogenic	0.9812	pathogenic	-1.723	Destabilizing	1.0	D	0.775	deleterious	N	0.50720408	None	None	I
L/S	0.9243	likely_pathogenic	0.9491	pathogenic	-3.004	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
L/T	0.7357	likely_pathogenic	0.8107	pathogenic	-2.622	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
L/V	0.1415	likely_benign	0.1622	benign	-1.462	Destabilizing	0.999	D	0.581	neutral	N	0.433484409	None	None	I
L/W	0.9825	likely_pathogenic	0.9888	pathogenic	-1.896	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
L/Y	0.9852	likely_pathogenic	0.9904	pathogenic	-1.61	Destabilizing	1.0	D	0.768	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.