TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1794	5605;5606;5607	chr2:178776484;178776483;178776482	chr2:179641211;179641210;179641209
N2AB	1794	5605;5606;5607	chr2:178776484;178776483;178776482	chr2:179641211;179641210;179641209
N2A	1794	5605;5606;5607	chr2:178776484;178776483;178776482	chr2:179641211;179641210;179641209
N2B	1748	5467;5468;5469	chr2:178776484;178776483;178776482	chr2:179641211;179641210;179641209
Novex-1	1748	5467;5468;5469	chr2:178776484;178776483;178776482	chr2:179641211;179641210;179641209
Novex-2	1748	5467;5468;5469	chr2:178776484;178776483;178776482	chr2:179641211;179641210;179641209
Novex-3	1794	5605;5606;5607	chr2:178776484;178776483;178776482	chr2:179641211;179641210;179641209

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-8
• Domain position: 92
• Structural Position: 178
• Q(SASA): 0.2531
• 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/A	rs774766261	-1.707	0.999	D	0.784	0.714	0.802620329787	gnomAD-2.1.1	1.62E-05	None	None	None	None	N	None	0	0	None	9.93E-05	0	None	0	None	0	1.77E-05	1.64258E-04
V/A	rs774766261	-1.707	0.999	D	0.784	0.714	0.802620329787	gnomAD-4.0.0	1.12418E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41196E-04	1.42837E-05	0	3.02499E-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
V/A	0.9246	likely_pathogenic	0.8769	pathogenic	-1.778	Destabilizing	0.999	D	0.784	deleterious	D	0.808561471	None	None	N
V/C	0.9758	likely_pathogenic	0.9646	pathogenic	-1.781	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/D	0.9992	likely_pathogenic	0.9985	pathogenic	-2.163	Highly Destabilizing	1.0	D	0.915	deleterious	D	0.807803822	None	None	N
V/E	0.9959	likely_pathogenic	0.9938	pathogenic	-2.101	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
V/F	0.9592	likely_pathogenic	0.8806	pathogenic	-1.342	Destabilizing	1.0	D	0.921	deleterious	D	0.808561471	None	None	N
V/G	0.9686	likely_pathogenic	0.9498	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.901	deleterious	D	0.807803822	None	None	N
V/H	0.999	likely_pathogenic	0.9974	pathogenic	-1.537	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/I	0.1552	likely_benign	0.1339	benign	-0.903	Destabilizing	0.997	D	0.749	deleterious	D	0.648475588	None	None	N
V/K	0.9979	likely_pathogenic	0.9955	pathogenic	-1.373	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
V/L	0.8359	likely_pathogenic	0.6718	pathogenic	-0.903	Destabilizing	0.997	D	0.792	deleterious	D	0.718613711	None	None	N
V/M	0.8878	likely_pathogenic	0.7844	pathogenic	-1.083	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/N	0.9951	likely_pathogenic	0.9922	pathogenic	-1.431	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
V/P	0.995	likely_pathogenic	0.9921	pathogenic	-1.165	Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
V/Q	0.9952	likely_pathogenic	0.9902	pathogenic	-1.581	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
V/R	0.9948	likely_pathogenic	0.9894	pathogenic	-0.946	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
V/S	0.9682	likely_pathogenic	0.9575	pathogenic	-1.991	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/T	0.9156	likely_pathogenic	0.8971	pathogenic	-1.817	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.998	pathogenic	-1.532	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/Y	0.9974	likely_pathogenic	0.9928	pathogenic	-1.213	Destabilizing	1.0	D	0.924	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.