TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21662	65209;65210;65211	chr2:178584567;178584566;178584565	chr2:179449294;179449293;179449292
N2AB	20021	60286;60287;60288	chr2:178584567;178584566;178584565	chr2:179449294;179449293;179449292
N2A	19094	57505;57506;57507	chr2:178584567;178584566;178584565	chr2:179449294;179449293;179449292
N2B	12597	38014;38015;38016	chr2:178584567;178584566;178584565	chr2:179449294;179449293;179449292
Novex-1	12722	38389;38390;38391	chr2:178584567;178584566;178584565	chr2:179449294;179449293;179449292
Novex-2	12789	38590;38591;38592	chr2:178584567;178584566;178584565	chr2:179449294;179449293;179449292
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: Fn3-45
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2869
• Predicted PPI site: N

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	rs1368089730	-1.275	0.979	N	0.628	0.308	0.260735089382	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.82E-05	None	0	0	None	0	None	0	0	0
E/D	rs1368089730	-1.275	0.979	N	0.628	0.308	0.260735089382	gnomAD-4.0.0	3.19107E-06	None	None	None	None	N	None	0	4.58253E-05	None	0	0	None	0	0	0	0	0
E/G	None	None	0.919	N	0.735	0.321	0.364342057095	gnomAD-4.0.0	1.59544E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43616E-05	0
E/K	rs2048514000	None	0.958	N	0.626	0.351	0.284150004643	gnomAD-4.0.0	3.42543E-06	None	None	None	None	N	None	0	0	None	0	1.01235E-04	None	0	0	9.00387E-07	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	0.108	likely_benign	0.1028	benign	-0.743	Destabilizing	0.067	N	0.439	neutral	N	0.426333858	None	None	N
E/C	0.778	likely_pathogenic	0.7664	pathogenic	-0.44	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
E/D	0.4377	ambiguous	0.4199	ambiguous	-1.227	Destabilizing	0.979	D	0.628	neutral	N	0.484308479	None	None	N
E/F	0.8425	likely_pathogenic	0.8422	pathogenic	-0.653	Destabilizing	0.995	D	0.855	deleterious	None	None	None	None	N
E/G	0.2763	likely_benign	0.2588	benign	-1.07	Destabilizing	0.919	D	0.735	prob.delet.	N	0.484308479	None	None	N
E/H	0.6742	likely_pathogenic	0.6728	pathogenic	-1.084	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/I	0.3786	ambiguous	0.4084	ambiguous	0.133	Stabilizing	0.991	D	0.839	deleterious	None	None	None	None	N
E/K	0.2185	likely_benign	0.2322	benign	-0.737	Destabilizing	0.958	D	0.626	neutral	N	0.509667317	None	None	N
E/L	0.5233	ambiguous	0.5352	ambiguous	0.133	Stabilizing	0.982	D	0.783	deleterious	None	None	None	None	N
E/M	0.4792	ambiguous	0.4806	ambiguous	0.624	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/N	0.5457	ambiguous	0.5473	ambiguous	-1.005	Destabilizing	0.995	D	0.712	prob.delet.	None	None	None	None	N
E/P	0.2775	likely_benign	0.2701	benign	-0.137	Destabilizing	0.995	D	0.732	prob.delet.	None	None	None	None	N
E/Q	0.1405	likely_benign	0.142	benign	-0.908	Destabilizing	0.994	D	0.706	prob.neutral	N	0.497874243	None	None	N
E/R	0.351	ambiguous	0.3556	ambiguous	-0.646	Destabilizing	0.995	D	0.715	prob.delet.	None	None	None	None	N
E/S	0.2555	likely_benign	0.247	benign	-1.324	Destabilizing	0.938	D	0.623	neutral	None	None	None	None	N
E/T	0.3031	likely_benign	0.3107	benign	-1.059	Destabilizing	0.991	D	0.717	prob.delet.	None	None	None	None	N
E/V	0.2087	likely_benign	0.2263	benign	-0.137	Destabilizing	0.976	D	0.753	deleterious	N	0.498298318	None	None	N
E/W	0.9659	likely_pathogenic	0.9625	pathogenic	-0.597	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
E/Y	0.7638	likely_pathogenic	0.7644	pathogenic	-0.456	Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N

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.