TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21103	63532;63533;63534	chr2:178588100;178588099;178588098	chr2:179452827;179452826;179452825
N2AB	19462	58609;58610;58611	chr2:178588100;178588099;178588098	chr2:179452827;179452826;179452825
N2A	18535	55828;55829;55830	chr2:178588100;178588099;178588098	chr2:179452827;179452826;179452825
N2B	12038	36337;36338;36339	chr2:178588100;178588099;178588098	chr2:179452827;179452826;179452825
Novex-1	12163	36712;36713;36714	chr2:178588100;178588099;178588098	chr2:179452827;179452826;179452825
Novex-2	12230	36913;36914;36915	chr2:178588100;178588099;178588098	chr2:179452827;179452826;179452825
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-41
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.152
• 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
M/I	rs538999642	-0.213	0.004	N	0.243	0.107	0.308278614506	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
M/I	rs538999642	-0.213	0.004	N	0.243	0.107	0.308278614506	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
M/I	rs538999642	-0.213	0.004	N	0.243	0.107	0.308278614506	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
M/I	rs538999642	-0.213	0.004	N	0.243	0.107	0.308278614506	gnomAD-4.0.0	6.57229E-06	None	None	None	None	N	None	0	6.5445E-05	None	0	0	None	0	0	0	0	0
M/T	rs770900534	-1.806	0.549	N	0.589	0.221	0.514923749907	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
M/T	rs770900534	-1.806	0.549	N	0.589	0.221	0.514923749907	gnomAD-4.0.0	1.59315E-06	None	None	None	None	N	None	0	2.28822E-05	None	0	0	None	0	0	0	0	0
M/V	rs1444195248	-0.704	0.036	N	0.367	0.094	0.303781844768	gnomAD-2.1.1	7.16E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.57E-05	0
M/V	rs1444195248	-0.704	0.036	N	0.367	0.094	0.303781844768	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/V	rs1444195248	-0.704	0.036	N	0.367	0.094	0.303781844768	gnomAD-4.0.0	2.4802E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.64745E-04	8.47975E-07	0	3.20441E-05

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
M/A	0.6342	likely_pathogenic	0.6293	pathogenic	-2.19	Highly Destabilizing	0.4	N	0.515	neutral	None	None	None	None	N
M/C	0.6907	likely_pathogenic	0.687	pathogenic	-2.262	Highly Destabilizing	0.992	D	0.706	prob.neutral	None	None	None	None	N
M/D	0.9781	likely_pathogenic	0.9819	pathogenic	-2.201	Highly Destabilizing	0.972	D	0.731	prob.delet.	None	None	None	None	N
M/E	0.7768	likely_pathogenic	0.7744	pathogenic	-1.936	Destabilizing	0.972	D	0.679	prob.neutral	None	None	None	None	N
M/F	0.3254	likely_benign	0.3246	benign	-0.769	Destabilizing	0.617	D	0.587	neutral	None	None	None	None	N
M/G	0.8427	likely_pathogenic	0.8533	pathogenic	-2.687	Highly Destabilizing	0.766	D	0.695	prob.neutral	None	None	None	None	N
M/H	0.7311	likely_pathogenic	0.7178	pathogenic	-2.419	Highly Destabilizing	0.992	D	0.73	prob.delet.	None	None	None	None	N
M/I	0.4251	ambiguous	0.4529	ambiguous	-0.737	Destabilizing	0.004	N	0.243	neutral	N	0.461470726	None	None	N
M/K	0.3199	likely_benign	0.2892	benign	-1.389	Destabilizing	0.712	D	0.584	neutral	N	0.445213194	None	None	N
M/L	0.206	likely_benign	0.2296	benign	-0.737	Destabilizing	0.001	N	0.165	neutral	N	0.462950806	None	None	N
M/N	0.8454	likely_pathogenic	0.8535	pathogenic	-1.897	Destabilizing	0.972	D	0.697	prob.neutral	None	None	None	None	N
M/P	0.9954	likely_pathogenic	0.9967	pathogenic	-1.207	Destabilizing	0.972	D	0.698	prob.neutral	None	None	None	None	N
M/Q	0.4179	ambiguous	0.383	ambiguous	-1.518	Destabilizing	0.972	D	0.607	neutral	None	None	None	None	N
M/R	0.4069	ambiguous	0.3578	ambiguous	-1.61	Destabilizing	0.963	D	0.677	prob.neutral	N	0.430110456	None	None	N
M/S	0.6703	likely_pathogenic	0.673	pathogenic	-2.391	Highly Destabilizing	0.766	D	0.575	neutral	None	None	None	None	N
M/T	0.5197	ambiguous	0.5278	ambiguous	-1.994	Destabilizing	0.549	D	0.589	neutral	N	0.488387968	None	None	N
M/V	0.1487	likely_benign	0.1554	benign	-1.207	Destabilizing	0.036	N	0.367	neutral	N	0.491502844	None	None	N
M/W	0.699	likely_pathogenic	0.701	pathogenic	-1.15	Destabilizing	0.992	D	0.708	prob.delet.	None	None	None	None	N
M/Y	0.5204	ambiguous	0.5123	ambiguous	-1.111	Destabilizing	0.92	D	0.678	prob.neutral	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.