TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19657	59194;59195;59196	chr2:178593239;178593238;178593237	chr2:179457966;179457965;179457964
N2AB	18016	54271;54272;54273	chr2:178593239;178593238;178593237	chr2:179457966;179457965;179457964
N2A	17089	51490;51491;51492	chr2:178593239;178593238;178593237	chr2:179457966;179457965;179457964
N2B	10592	31999;32000;32001	chr2:178593239;178593238;178593237	chr2:179457966;179457965;179457964
Novex-1	10717	32374;32375;32376	chr2:178593239;178593238;178593237	chr2:179457966;179457965;179457964
Novex-2	10784	32575;32576;32577	chr2:178593239;178593238;178593237	chr2:179457966;179457965;179457964
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-30
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.1809
• 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
E/D	rs200728232	-1.487	0.977	N	0.409	0.308	0.407901774203	gnomAD-2.1.1	5.72E-05	None	None	None	None	I	None	5.7856E-04	5.67E-05	None	0	0	None	0	None	0	0	0
E/D	rs200728232	-1.487	0.977	N	0.409	0.308	0.407901774203	gnomAD-3.1.2	1.51184E-04	None	None	None	None	I	None	5.30734E-04	6.55E-05	0	0	0	None	0	0	0	0	0
E/D	rs200728232	-1.487	0.977	N	0.409	0.308	0.407901774203	gnomAD-4.0.0	2.91313E-05	None	None	None	None	I	None	5.60703E-04	5.00367E-05	None	0	0	None	0	0	0	0	3.20277E-05
E/K	None	None	0.955	N	0.419	0.273	0.369867359543	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.2974	likely_benign	0.2721	benign	-0.634	Destabilizing	0.977	D	0.537	neutral	N	0.467530443	None	None	I
E/C	0.8766	likely_pathogenic	0.8809	pathogenic	-0.412	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
E/D	0.76	likely_pathogenic	0.7643	pathogenic	-1.272	Destabilizing	0.977	D	0.409	neutral	N	0.506096037	None	None	I
E/F	0.887	likely_pathogenic	0.8871	pathogenic	-0.98	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
E/G	0.4953	ambiguous	0.4809	ambiguous	-0.935	Destabilizing	0.993	D	0.718	prob.delet.	N	0.499348088	None	None	I
E/H	0.8223	likely_pathogenic	0.8246	pathogenic	-1.243	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
E/I	0.3797	ambiguous	0.3818	ambiguous	0.164	Stabilizing	0.998	D	0.887	deleterious	None	None	None	None	I
E/K	0.2914	likely_benign	0.2718	benign	-0.498	Destabilizing	0.955	D	0.419	neutral	N	0.472000668	None	None	I
E/L	0.6499	likely_pathogenic	0.6358	pathogenic	0.164	Stabilizing	0.995	D	0.827	deleterious	None	None	None	None	I
E/M	0.4933	ambiguous	0.4876	ambiguous	0.629	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
E/N	0.7847	likely_pathogenic	0.7843	pathogenic	-0.743	Destabilizing	0.995	D	0.649	neutral	None	None	None	None	I
E/P	0.9953	likely_pathogenic	0.9958	pathogenic	-0.081	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	I
E/Q	0.1697	likely_benign	0.1642	benign	-0.652	Destabilizing	0.568	D	0.251	neutral	N	0.469100606	None	None	I
E/R	0.4758	ambiguous	0.4645	ambiguous	-0.563	Destabilizing	0.99	D	0.644	neutral	None	None	None	None	I
E/S	0.4773	ambiguous	0.4712	ambiguous	-1.116	Destabilizing	0.983	D	0.454	neutral	None	None	None	None	I
E/T	0.4272	ambiguous	0.4268	ambiguous	-0.848	Destabilizing	0.995	D	0.728	prob.delet.	None	None	None	None	I
E/V	0.2268	likely_benign	0.2213	benign	-0.081	Destabilizing	0.997	D	0.808	deleterious	N	0.474162303	None	None	I
E/W	0.9734	likely_pathogenic	0.9738	pathogenic	-1.095	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
E/Y	0.8763	likely_pathogenic	0.8792	pathogenic	-0.776	Destabilizing	0.999	D	0.869	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.