TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33682	101269;101270;101271	chr2:178535571;178535570;178535569	chr2:179400298;179400297;179400296
N2AB	32041	96346;96347;96348	chr2:178535571;178535570;178535569	chr2:179400298;179400297;179400296
N2A	31114	93565;93566;93567	chr2:178535571;178535570;178535569	chr2:179400298;179400297;179400296
N2B	24617	74074;74075;74076	chr2:178535571;178535570;178535569	chr2:179400298;179400297;179400296
Novex-1	24742	74449;74450;74451	chr2:178535571;178535570;178535569	chr2:179400298;179400297;179400296
Novex-2	24809	74650;74651;74652	chr2:178535571;178535570;178535569	chr2:179400298;179400297;179400296
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-159
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.12
• 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	rs768803095	-2.342	0.999	N	0.501	0.465	0.581818759506	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
V/A	rs768803095	-2.342	0.999	N	0.501	0.465	0.581818759506	gnomAD-4.0.0	3.18241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85812E-06	1.43271E-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	0.869	likely_pathogenic	0.7819	pathogenic	-1.81	Destabilizing	0.999	D	0.501	neutral	N	0.483262655	None	None	N
V/C	0.972	likely_pathogenic	0.9626	pathogenic	-1.389	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/D	0.9989	likely_pathogenic	0.9979	pathogenic	-1.821	Destabilizing	1.0	D	0.861	deleterious	N	0.509778655	None	None	N
V/E	0.993	likely_pathogenic	0.9876	pathogenic	-1.62	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/F	0.7959	likely_pathogenic	0.6446	pathogenic	-0.978	Destabilizing	1.0	D	0.801	deleterious	N	0.492175714	None	None	N
V/G	0.9754	likely_pathogenic	0.9552	pathogenic	-2.339	Highly Destabilizing	1.0	D	0.841	deleterious	N	0.511801625	None	None	N
V/H	0.9979	likely_pathogenic	0.9959	pathogenic	-1.902	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/I	0.1155	likely_benign	0.1013	benign	-0.358	Destabilizing	0.11	N	0.209	neutral	N	0.448499507	None	None	N
V/K	0.9943	likely_pathogenic	0.99	pathogenic	-1.517	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
V/L	0.66	likely_pathogenic	0.5169	ambiguous	-0.358	Destabilizing	0.968	D	0.477	neutral	N	0.49182621	None	None	N
V/M	0.6389	likely_pathogenic	0.4945	ambiguous	-0.428	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
V/N	0.9967	likely_pathogenic	0.9935	pathogenic	-1.736	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/P	0.998	likely_pathogenic	0.9967	pathogenic	-0.812	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/Q	0.9915	likely_pathogenic	0.9845	pathogenic	-1.584	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/R	0.9892	likely_pathogenic	0.9809	pathogenic	-1.363	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
V/S	0.9838	likely_pathogenic	0.9699	pathogenic	-2.433	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/T	0.9053	likely_pathogenic	0.8612	pathogenic	-2.072	Highly Destabilizing	0.997	D	0.609	neutral	None	None	None	None	N
V/W	0.9972	likely_pathogenic	0.9935	pathogenic	-1.369	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/Y	0.9885	likely_pathogenic	0.9762	pathogenic	-0.988	Destabilizing	1.0	D	0.818	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.