TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30423	91492;91493;91494	chr2:178551633;178551632;178551631	chr2:179416360;179416359;179416358
N2AB	28782	86569;86570;86571	chr2:178551633;178551632;178551631	chr2:179416360;179416359;179416358
N2A	27855	83788;83789;83790	chr2:178551633;178551632;178551631	chr2:179416360;179416359;179416358
N2B	21358	64297;64298;64299	chr2:178551633;178551632;178551631	chr2:179416360;179416359;179416358
Novex-1	21483	64672;64673;64674	chr2:178551633;178551632;178551631	chr2:179416360;179416359;179416358
Novex-2	21550	64873;64874;64875	chr2:178551633;178551632;178551631	chr2:179416360;179416359;179416358
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-110
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.0923
• 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/I	rs1699485019	None	0.994	N	0.587	0.245	0.286848849266	gnomAD-4.0.0	1.05561E-05	None	None	None	None	N	None	0	0	None	0	3.83024E-04	None	0	0	0	0	0
V/L	None	None	0.994	N	0.617	0.255	0.246773566709	gnomAD-4.0.0	7.03737E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.15498E-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
V/A	0.6881	likely_pathogenic	0.6751	pathogenic	-1.635	Destabilizing	0.997	D	0.586	neutral	N	0.485691593	None	None	N
V/C	0.9033	likely_pathogenic	0.9038	pathogenic	-1.448	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
V/D	0.9937	likely_pathogenic	0.9944	pathogenic	-2.596	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
V/E	0.9849	likely_pathogenic	0.9864	pathogenic	-2.578	Highly Destabilizing	0.999	D	0.814	deleterious	N	0.475437314	None	None	N
V/F	0.9293	likely_pathogenic	0.9289	pathogenic	-1.327	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
V/G	0.9041	likely_pathogenic	0.904	pathogenic	-1.958	Destabilizing	0.999	D	0.789	deleterious	N	0.469110151	None	None	N
V/H	0.9968	likely_pathogenic	0.9972	pathogenic	-1.511	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
V/I	0.1118	likely_benign	0.1076	benign	-0.817	Destabilizing	0.994	D	0.587	neutral	N	0.404710579	None	None	N
V/K	0.992	likely_pathogenic	0.9931	pathogenic	-1.406	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
V/L	0.7139	likely_pathogenic	0.691	pathogenic	-0.817	Destabilizing	0.994	D	0.617	neutral	N	0.456984839	None	None	N
V/M	0.6801	likely_pathogenic	0.6681	pathogenic	-0.695	Destabilizing	0.999	D	0.652	prob.neutral	None	None	None	None	N
V/N	0.9738	likely_pathogenic	0.9767	pathogenic	-1.415	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
V/P	0.9147	likely_pathogenic	0.9015	pathogenic	-1.059	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
V/Q	0.9845	likely_pathogenic	0.9859	pathogenic	-1.623	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
V/R	0.9848	likely_pathogenic	0.9871	pathogenic	-0.894	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
V/S	0.8825	likely_pathogenic	0.8851	pathogenic	-1.819	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
V/T	0.6712	likely_pathogenic	0.66	pathogenic	-1.702	Destabilizing	0.998	D	0.588	neutral	None	None	None	None	N
V/W	0.9985	likely_pathogenic	0.9985	pathogenic	-1.602	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/Y	0.9938	likely_pathogenic	0.9942	pathogenic	-1.296	Destabilizing	0.999	D	0.773	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.