TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2163	6712;6713;6714	chr2:178775377;178775376;178775375	chr2:179640104;179640103;179640102
N2AB	2163	6712;6713;6714	chr2:178775377;178775376;178775375	chr2:179640104;179640103;179640102
N2A	2163	6712;6713;6714	chr2:178775377;178775376;178775375	chr2:179640104;179640103;179640102
N2B	2117	6574;6575;6576	chr2:178775377;178775376;178775375	chr2:179640104;179640103;179640102
Novex-1	2117	6574;6575;6576	chr2:178775377;178775376;178775375	chr2:179640104;179640103;179640102
Novex-2	2117	6574;6575;6576	chr2:178775377;178775376;178775375	chr2:179640104;179640103;179640102
Novex-3	2163	6712;6713;6714	chr2:178775377;178775376;178775375	chr2:179640104;179640103;179640102

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-10
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.4029
• 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
H/L	rs765031763	0.756	1.0	N	0.777	0.642	0.667488003546	gnomAD-2.1.1	3.98E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.82E-06	0
H/L	rs765031763	0.756	1.0	N	0.777	0.642	0.667488003546	gnomAD-4.0.0	4.78868E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29509E-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
H/A	0.887	likely_pathogenic	0.9134	pathogenic	-0.485	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	I
H/C	0.7771	likely_pathogenic	0.7788	pathogenic	0.176	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
H/D	0.9026	likely_pathogenic	0.9263	pathogenic	-0.153	Destabilizing	1.0	D	0.749	deleterious	N	0.483540994	None	None	I
H/E	0.9119	likely_pathogenic	0.9357	pathogenic	-0.079	Destabilizing	0.999	D	0.564	neutral	None	None	None	None	I
H/F	0.7737	likely_pathogenic	0.7944	pathogenic	0.538	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
H/G	0.9275	likely_pathogenic	0.9453	pathogenic	-0.823	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	I
H/I	0.9219	likely_pathogenic	0.937	pathogenic	0.421	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
H/K	0.8871	likely_pathogenic	0.9117	pathogenic	-0.332	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
H/L	0.5941	likely_pathogenic	0.6347	pathogenic	0.421	Stabilizing	1.0	D	0.777	deleterious	N	0.501123153	None	None	I
H/M	0.9098	likely_pathogenic	0.9239	pathogenic	0.252	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
H/N	0.4956	ambiguous	0.5714	pathogenic	-0.418	Destabilizing	0.999	D	0.557	neutral	N	0.468760735	None	None	I
H/P	0.8423	likely_pathogenic	0.8672	pathogenic	0.142	Stabilizing	1.0	D	0.807	deleterious	N	0.509575668	None	None	I
H/Q	0.7501	likely_pathogenic	0.802	pathogenic	-0.237	Destabilizing	1.0	D	0.687	prob.neutral	N	0.464832961	None	None	I
H/R	0.683	likely_pathogenic	0.7368	pathogenic	-0.772	Destabilizing	1.0	D	0.671	neutral	N	0.468534326	None	None	I
H/S	0.7353	likely_pathogenic	0.7886	pathogenic	-0.481	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
H/T	0.8654	likely_pathogenic	0.8991	pathogenic	-0.299	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
H/V	0.8782	likely_pathogenic	0.903	pathogenic	0.142	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
H/W	0.8494	likely_pathogenic	0.8552	pathogenic	0.784	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
H/Y	0.4268	ambiguous	0.4587	ambiguous	0.923	Stabilizing	0.999	D	0.559	neutral	N	0.499056641	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.