TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33579	100960;100961;100962	chr2:178536012;178536011;178536010	chr2:179400739;179400738;179400737
N2AB	31938	96037;96038;96039	chr2:178536012;178536011;178536010	chr2:179400739;179400738;179400737
N2A	31011	93256;93257;93258	chr2:178536012;178536011;178536010	chr2:179400739;179400738;179400737
N2B	24514	73765;73766;73767	chr2:178536012;178536011;178536010	chr2:179400739;179400738;179400737
Novex-1	24639	74140;74141;74142	chr2:178536012;178536011;178536010	chr2:179400739;179400738;179400737
Novex-2	24706	74341;74342;74343	chr2:178536012;178536011;178536010	chr2:179400739;179400738;179400737
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-158
• Domain position: 84
• Structural Position: 166
• Q(SASA): 0.2896
• 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/M	rs1344390830	-0.288	0.971	N	0.563	0.352	0.585593966701	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	1.14758E-04	0	None	0	0	None	0	None	0	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	0.538	ambiguous	0.4224	ambiguous	-1.064	Destabilizing	0.746	D	0.529	neutral	N	0.442360182	None	None	I
V/C	0.8936	likely_pathogenic	0.8766	pathogenic	-0.921	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	I
V/D	0.9059	likely_pathogenic	0.8441	pathogenic	-0.04	Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	I
V/E	0.8144	likely_pathogenic	0.7421	pathogenic	-0.034	Destabilizing	0.984	D	0.727	prob.delet.	N	0.504179432	None	None	I
V/F	0.493	ambiguous	0.4451	ambiguous	-0.744	Destabilizing	0.984	D	0.623	neutral	None	None	None	None	I
V/G	0.7872	likely_pathogenic	0.6965	pathogenic	-1.365	Destabilizing	0.998	D	0.749	deleterious	N	0.489077052	None	None	I
V/H	0.9318	likely_pathogenic	0.9053	pathogenic	-0.749	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	I
V/I	0.0841	likely_benign	0.0904	benign	-0.356	Destabilizing	0.002	N	0.162	neutral	None	None	None	None	I
V/K	0.8018	likely_pathogenic	0.752	pathogenic	-0.634	Destabilizing	0.983	D	0.733	prob.delet.	None	None	None	None	I
V/L	0.4494	ambiguous	0.421	ambiguous	-0.356	Destabilizing	0.091	N	0.407	neutral	N	0.504046146	None	None	I
V/M	0.3247	likely_benign	0.3227	benign	-0.458	Destabilizing	0.971	D	0.563	neutral	N	0.493369466	None	None	I
V/N	0.8059	likely_pathogenic	0.7514	pathogenic	-0.496	Destabilizing	0.963	D	0.782	deleterious	None	None	None	None	I
V/P	0.9942	likely_pathogenic	0.9899	pathogenic	-0.555	Destabilizing	0.963	D	0.735	prob.delet.	None	None	None	None	I
V/Q	0.7693	likely_pathogenic	0.6953	pathogenic	-0.587	Destabilizing	0.992	D	0.741	deleterious	None	None	None	None	I
V/R	0.7642	likely_pathogenic	0.6988	pathogenic	-0.27	Destabilizing	0.997	D	0.779	deleterious	None	None	None	None	I
V/S	0.6832	likely_pathogenic	0.5967	pathogenic	-1.16	Destabilizing	0.985	D	0.66	neutral	None	None	None	None	I
V/T	0.4942	ambiguous	0.438	ambiguous	-1.023	Destabilizing	0.792	D	0.544	neutral	None	None	None	None	I
V/W	0.9824	likely_pathogenic	0.9752	pathogenic	-0.854	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
V/Y	0.9022	likely_pathogenic	0.8791	pathogenic	-0.538	Destabilizing	0.997	D	0.617	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.