TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17139	51640;51641;51642	chr2:178610111;178610110;178610109	chr2:179474838;179474837;179474836
N2AB	15498	46717;46718;46719	chr2:178610111;178610110;178610109	chr2:179474838;179474837;179474836
N2A	14571	43936;43937;43938	chr2:178610111;178610110;178610109	chr2:179474838;179474837;179474836
N2B	8074	24445;24446;24447	chr2:178610111;178610110;178610109	chr2:179474838;179474837;179474836
Novex-1	8199	24820;24821;24822	chr2:178610111;178610110;178610109	chr2:179474838;179474837;179474836
Novex-2	8266	25021;25022;25023	chr2:178610111;178610110;178610109	chr2:179474838;179474837;179474836
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-12
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.2344
• 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/L	rs758008217	-0.369	0.056	N	0.47	0.07	0.218845423259	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
V/L	rs758008217	-0.369	0.056	N	0.47	0.07	0.218845423259	gnomAD-4.0.0	7.53044E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.89778E-06	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	0.6684	likely_pathogenic	0.7356	pathogenic	-1.859	Destabilizing	0.457	N	0.477	neutral	N	0.483162255	None	None	N
V/C	0.8877	likely_pathogenic	0.8991	pathogenic	-1.15	Destabilizing	0.989	D	0.769	deleterious	None	None	None	None	N
V/D	0.9867	likely_pathogenic	0.9919	pathogenic	-2.319	Highly Destabilizing	0.857	D	0.892	deleterious	N	0.502533957	None	None	N
V/E	0.9417	likely_pathogenic	0.9552	pathogenic	-2.089	Highly Destabilizing	0.888	D	0.865	deleterious	None	None	None	None	N
V/F	0.5881	likely_pathogenic	0.6245	pathogenic	-1.13	Destabilizing	0.747	D	0.785	deleterious	N	0.475528932	None	None	N
V/G	0.902	likely_pathogenic	0.927	pathogenic	-2.358	Highly Destabilizing	0.857	D	0.891	deleterious	N	0.502533957	None	None	N
V/H	0.9745	likely_pathogenic	0.9797	pathogenic	-1.914	Destabilizing	0.989	D	0.859	deleterious	None	None	None	None	N
V/I	0.0749	likely_benign	0.0791	benign	-0.462	Destabilizing	0.003	N	0.2	neutral	N	0.428952876	None	None	N
V/K	0.956	likely_pathogenic	0.9656	pathogenic	-1.511	Destabilizing	0.888	D	0.868	deleterious	None	None	None	None	N
V/L	0.3603	ambiguous	0.4017	ambiguous	-0.462	Destabilizing	0.056	N	0.47	neutral	N	0.491097413	None	None	N
V/M	0.3276	likely_benign	0.3715	ambiguous	-0.422	Destabilizing	0.797	D	0.675	prob.neutral	None	None	None	None	N
V/N	0.9436	likely_pathogenic	0.9649	pathogenic	-1.872	Destabilizing	0.96	D	0.88	deleterious	None	None	None	None	N
V/P	0.9921	likely_pathogenic	0.9933	pathogenic	-0.903	Destabilizing	0.96	D	0.864	deleterious	None	None	None	None	N
V/Q	0.9219	likely_pathogenic	0.9357	pathogenic	-1.706	Destabilizing	0.96	D	0.86	deleterious	None	None	None	None	N
V/R	0.9435	likely_pathogenic	0.954	pathogenic	-1.407	Destabilizing	0.888	D	0.881	deleterious	None	None	None	None	N
V/S	0.8675	likely_pathogenic	0.9146	pathogenic	-2.452	Highly Destabilizing	0.888	D	0.839	deleterious	None	None	None	None	N
V/T	0.6315	likely_pathogenic	0.6866	pathogenic	-2.074	Highly Destabilizing	0.528	D	0.609	neutral	None	None	None	None	N
V/W	0.9881	likely_pathogenic	0.9882	pathogenic	-1.552	Destabilizing	0.989	D	0.82	deleterious	None	None	None	None	N
V/Y	0.9385	likely_pathogenic	0.9465	pathogenic	-1.142	Destabilizing	0.888	D	0.779	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.