TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35013	105262;105263;105264	chr2:178531578;178531577;178531576	chr2:179396305;179396304;179396303
N2AB	33372	100339;100340;100341	chr2:178531578;178531577;178531576	chr2:179396305;179396304;179396303
N2A	32445	97558;97559;97560	chr2:178531578;178531577;178531576	chr2:179396305;179396304;179396303
N2B	25948	78067;78068;78069	chr2:178531578;178531577;178531576	chr2:179396305;179396304;179396303
Novex-1	26073	78442;78443;78444	chr2:178531578;178531577;178531576	chr2:179396305;179396304;179396303
Novex-2	26140	78643;78644;78645	chr2:178531578;178531577;178531576	chr2:179396305;179396304;179396303
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Ig-163
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.3048
• 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
R/C	rs568460311	-1.613	1.0	N	0.816	0.368	None	gnomAD-2.1.1	9.27E-05	None	None	None	None	N	None	2.06714E-04	2.83E-05	None	0	4.10256E-04	None	0	None	8E-05	7.8E-05	0
R/C	rs568460311	-1.613	1.0	N	0.816	0.368	None	gnomAD-3.1.2	9.2E-05	None	None	None	None	N	None	1.69033E-04	6.54E-05	0	0	3.85356E-04	None	0	0	2.94E-05	0	9.57854E-04
R/C	rs568460311	-1.613	1.0	N	0.816	0.368	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/C	rs568460311	-1.613	1.0	N	0.816	0.368	None	gnomAD-4.0.0	3.65566E-05	None	None	None	None	N	None	1.86637E-04	3.33189E-05	None	0	2.22876E-04	None	9.37266E-05	0	1.61035E-05	0	1.28033E-04
R/H	rs779484675	-1.995	1.0	N	0.751	0.421	None	gnomAD-2.1.1	3.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.96066E-04	None	0	1.77E-05	0
R/H	rs779484675	-1.995	1.0	N	0.751	0.421	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs779484675	-1.995	1.0	N	0.751	0.421	None	gnomAD-4.0.0	2.85035E-05	None	None	None	None	N	None	1.33518E-05	1.6665E-05	None	0	0	None	1.5623E-05	0	2.11883E-05	1.97624E-04	0
R/P	None	None	1.0	N	0.781	0.527	0.41441075005	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92604E-04	None	0	0	0	0	0
R/P	None	None	1.0	N	0.781	0.527	0.41441075005	gnomAD-4.0.0	6.57237E-06	None	None	None	None	N	None	0	0	None	0	1.92604E-04	None	0	0	0	0	0
R/S	rs568460311	-2.031	1.0	N	0.743	0.429	0.262662153117	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/S	rs568460311	-2.031	1.0	N	0.743	0.429	0.262662153117	gnomAD-4.0.0	1.3683E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31868E-05	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
R/A	0.9561	likely_pathogenic	0.9741	pathogenic	-1.484	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
R/C	0.6668	likely_pathogenic	0.7745	pathogenic	-1.467	Destabilizing	1.0	D	0.816	deleterious	N	0.505637217	None	None	N
R/D	0.9925	likely_pathogenic	0.9961	pathogenic	-0.146	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
R/E	0.9026	likely_pathogenic	0.9419	pathogenic	0.009	Stabilizing	0.999	D	0.607	neutral	None	None	None	None	N
R/F	0.958	likely_pathogenic	0.9752	pathogenic	-1.171	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
R/G	0.9292	likely_pathogenic	0.9608	pathogenic	-1.806	Destabilizing	1.0	D	0.733	prob.delet.	N	0.475544342	None	None	N
R/H	0.3493	ambiguous	0.4775	ambiguous	-1.808	Destabilizing	1.0	D	0.751	deleterious	N	0.510312318	None	None	N
R/I	0.8827	likely_pathogenic	0.923	pathogenic	-0.592	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
R/K	0.3838	ambiguous	0.5022	ambiguous	-1.174	Destabilizing	0.998	D	0.533	neutral	None	None	None	None	N
R/L	0.7958	likely_pathogenic	0.877	pathogenic	-0.592	Destabilizing	1.0	D	0.733	prob.delet.	N	0.496612302	None	None	N
R/M	0.886	likely_pathogenic	0.9303	pathogenic	-0.947	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
R/N	0.9779	likely_pathogenic	0.9891	pathogenic	-0.705	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
R/P	0.9982	likely_pathogenic	0.999	pathogenic	-0.872	Destabilizing	1.0	D	0.781	deleterious	N	0.475797832	None	None	N
R/Q	0.3396	likely_benign	0.4763	ambiguous	-0.868	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
R/S	0.9523	likely_pathogenic	0.9755	pathogenic	-1.731	Destabilizing	1.0	D	0.743	deleterious	N	0.450127864	None	None	N
R/T	0.8897	likely_pathogenic	0.9352	pathogenic	-1.376	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
R/V	0.8982	likely_pathogenic	0.9338	pathogenic	-0.872	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
R/W	0.7158	likely_pathogenic	0.7931	pathogenic	-0.651	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
R/Y	0.8894	likely_pathogenic	0.9297	pathogenic	-0.439	Destabilizing	1.0	D	0.817	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.