TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1478	4657;4658;4659	chr2:178777752;178777751;178777750	chr2:179642479;179642478;179642477
N2AB	1478	4657;4658;4659	chr2:178777752;178777751;178777750	chr2:179642479;179642478;179642477
N2A	1478	4657;4658;4659	chr2:178777752;178777751;178777750	chr2:179642479;179642478;179642477
N2B	1432	4519;4520;4521	chr2:178777752;178777751;178777750	chr2:179642479;179642478;179642477
Novex-1	1432	4519;4520;4521	chr2:178777752;178777751;178777750	chr2:179642479;179642478;179642477
Novex-2	1432	4519;4520;4521	chr2:178777752;178777751;178777750	chr2:179642479;179642478;179642477
Novex-3	1478	4657;4658;4659	chr2:178777752;178777751;178777750	chr2:179642479;179642478;179642477

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-6
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1788
• 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/F	rs1175803570	-1.625	1.0	N	0.839	0.515	0.594452868026	gnomAD-2.1.1	3.99E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.82E-06	0
L/F	rs1175803570	-1.625	1.0	N	0.839	0.515	0.594452868026	gnomAD-4.0.0	1.36821E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79866E-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
L/A	0.7695	likely_pathogenic	0.8254	pathogenic	-2.758	Highly Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	I
L/C	0.7362	likely_pathogenic	0.7789	pathogenic	-2.327	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
L/D	0.9984	likely_pathogenic	0.9989	pathogenic	-3.099	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
L/E	0.9873	likely_pathogenic	0.991	pathogenic	-2.837	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
L/F	0.6558	likely_pathogenic	0.7129	pathogenic	-1.648	Destabilizing	1.0	D	0.839	deleterious	N	0.508641744	None	None	I
L/G	0.9678	likely_pathogenic	0.9768	pathogenic	-3.355	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
L/H	0.9717	likely_pathogenic	0.978	pathogenic	-2.793	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
L/I	0.1411	likely_benign	0.1627	benign	-1.011	Destabilizing	0.999	D	0.691	prob.neutral	N	0.486180307	None	None	I
L/K	0.99	likely_pathogenic	0.9915	pathogenic	-2.175	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
L/M	0.2117	likely_benign	0.2444	benign	-1.147	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
L/N	0.9819	likely_pathogenic	0.9873	pathogenic	-2.632	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	I
L/P	0.9988	likely_pathogenic	0.999	pathogenic	-1.576	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
L/Q	0.9431	likely_pathogenic	0.9536	pathogenic	-2.434	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
L/R	0.9788	likely_pathogenic	0.9818	pathogenic	-1.939	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
L/S	0.9291	likely_pathogenic	0.9507	pathogenic	-3.384	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.528333096	None	None	I
L/T	0.7423	likely_pathogenic	0.8031	pathogenic	-2.958	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
L/V	0.1263	likely_benign	0.148	benign	-1.576	Destabilizing	0.999	D	0.689	prob.neutral	N	0.423398995	None	None	I
L/W	0.9691	likely_pathogenic	0.9751	pathogenic	-2.022	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
L/Y	0.9635	likely_pathogenic	0.9708	pathogenic	-1.763	Destabilizing	1.0	D	0.838	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.