TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14794	44605;44606;44607	chr2:178629345;178629344;178629343	chr2:179494072;179494071;179494070
N2AB	13153	39682;39683;39684	chr2:178629345;178629344;178629343	chr2:179494072;179494071;179494070
N2A	12226	36901;36902;36903	chr2:178629345;178629344;178629343	chr2:179494072;179494071;179494070
N2B	5729	17410;17411;17412	chr2:178629345;178629344;178629343	chr2:179494072;179494071;179494070
Novex-1	5854	17785;17786;17787	chr2:178629345;178629344;178629343	chr2:179494072;179494071;179494070
Novex-2	5921	17986;17987;17988	chr2:178629345;178629344;178629343	chr2:179494072;179494071;179494070
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-99
• Domain position: 30
• Structural Position: 46
• Q(SASA): 0.2225
• 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
V/G	rs779834438	-2.645	1.0	N	0.856	0.676	0.815322740875	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/G	rs779834438	-2.645	1.0	N	0.856	0.676	0.815322740875	gnomAD-4.0.0	2.73842E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.63876E-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
V/A	0.3313	likely_benign	0.3771	ambiguous	-1.676	Destabilizing	0.999	D	0.642	neutral	D	0.582767262	None	None	N
V/C	0.88	likely_pathogenic	0.9075	pathogenic	-0.997	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/D	0.9556	likely_pathogenic	0.9789	pathogenic	-1.904	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/E	0.8994	likely_pathogenic	0.9394	pathogenic	-1.815	Destabilizing	1.0	D	0.862	deleterious	D	0.730489284	None	None	N
V/F	0.6447	likely_pathogenic	0.7231	pathogenic	-1.178	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/G	0.6307	likely_pathogenic	0.698	pathogenic	-2.069	Highly Destabilizing	1.0	D	0.856	deleterious	N	0.511351758	None	None	N
V/H	0.9692	likely_pathogenic	0.9828	pathogenic	-1.672	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/I	0.1446	likely_benign	0.1604	benign	-0.648	Destabilizing	0.998	D	0.642	neutral	None	None	None	None	N
V/K	0.9132	likely_pathogenic	0.9497	pathogenic	-1.428	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/L	0.572	likely_pathogenic	0.6231	pathogenic	-0.648	Destabilizing	0.997	D	0.671	neutral	D	0.580311369	None	None	N
V/M	0.429	ambiguous	0.5044	ambiguous	-0.496	Destabilizing	1.0	D	0.751	deleterious	D	0.693095501	None	None	N
V/N	0.9061	likely_pathogenic	0.9504	pathogenic	-1.367	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/P	0.8462	likely_pathogenic	0.8901	pathogenic	-0.959	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/Q	0.8894	likely_pathogenic	0.929	pathogenic	-1.425	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/R	0.8763	likely_pathogenic	0.9218	pathogenic	-1.024	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/S	0.6365	likely_pathogenic	0.7077	pathogenic	-1.862	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/T	0.3957	ambiguous	0.4443	ambiguous	-1.652	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
V/W	0.9854	likely_pathogenic	0.9903	pathogenic	-1.506	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9523	likely_pathogenic	0.9674	pathogenic	-1.157	Destabilizing	1.0	D	0.799	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.