TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8352	25279;25280;25281	chr2:178717952;178717951;178717950	chr2:179582679;179582678;179582677
N2AB	8035	24328;24329;24330	chr2:178717952;178717951;178717950	chr2:179582679;179582678;179582677
N2A	7108	21547;21548;21549	chr2:178717952;178717951;178717950	chr2:179582679;179582678;179582677
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-68
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3289
• Predicted PPI site: I

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	rs750897859	-0.232	0.001	N	0.257	0.194	0.358340041657	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/L	rs750897859	-0.232	0.001	N	0.257	0.194	0.358340041657	gnomAD-4.0.0	9.58653E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.72491E-05	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	0.1433	likely_benign	0.1609	benign	-1.097	Destabilizing	None	N	0.083	neutral	N	0.4858416	None	None	I
V/C	0.6581	likely_pathogenic	0.7059	pathogenic	-0.794	Destabilizing	0.893	D	0.428	neutral	None	None	None	None	I
V/D	0.1936	likely_benign	0.2207	benign	-0.716	Destabilizing	0.086	N	0.543	neutral	N	0.48688175	None	None	I
V/E	0.1649	likely_benign	0.1786	benign	-0.731	Destabilizing	0.008	N	0.428	neutral	None	None	None	None	I
V/F	0.1075	likely_benign	0.1187	benign	-0.777	Destabilizing	0.333	N	0.467	neutral	N	0.500600409	None	None	I
V/G	0.1772	likely_benign	0.2047	benign	-1.388	Destabilizing	0.05	N	0.459	neutral	D	0.535443701	None	None	I
V/H	0.3107	likely_benign	0.3403	ambiguous	-0.884	Destabilizing	0.489	N	0.505	neutral	None	None	None	None	I
V/I	0.0748	likely_benign	0.0767	benign	-0.419	Destabilizing	None	N	0.145	neutral	N	0.463986248	None	None	I
V/K	0.2117	likely_benign	0.242	benign	-0.96	Destabilizing	0.001	N	0.304	neutral	None	None	None	None	I
V/L	0.125	likely_benign	0.1343	benign	-0.419	Destabilizing	0.001	N	0.257	neutral	N	0.455366765	None	None	I
V/M	0.1274	likely_benign	0.1317	benign	-0.392	Destabilizing	0.321	N	0.382	neutral	None	None	None	None	I
V/N	0.1414	likely_benign	0.1604	benign	-0.754	Destabilizing	None	N	0.371	neutral	None	None	None	None	I
V/P	0.7088	likely_pathogenic	0.7893	pathogenic	-0.609	Destabilizing	0.026	N	0.504	neutral	None	None	None	None	I
V/Q	0.1922	likely_benign	0.212	benign	-0.908	Destabilizing	0.002	N	0.345	neutral	None	None	None	None	I
V/R	0.1814	likely_benign	0.2091	benign	-0.471	Destabilizing	0.001	N	0.374	neutral	None	None	None	None	I
V/S	0.1361	likely_benign	0.1535	benign	-1.27	Destabilizing	0.021	N	0.436	neutral	None	None	None	None	I
V/T	0.1258	likely_benign	0.1343	benign	-1.175	Destabilizing	None	N	0.095	neutral	None	None	None	None	I
V/W	0.6582	likely_pathogenic	0.6976	pathogenic	-0.949	Destabilizing	0.976	D	0.525	neutral	None	None	None	None	I
V/Y	0.3449	ambiguous	0.3716	ambiguous	-0.651	Destabilizing	0.573	D	0.463	neutral	None	None	None	None	I

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.