TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25285	76078;76079;76080	chr2:178570279;178570278;178570277	chr2:179435006;179435005;179435004
N2AB	23644	71155;71156;71157	chr2:178570279;178570278;178570277	chr2:179435006;179435005;179435004
N2A	22717	68374;68375;68376	chr2:178570279;178570278;178570277	chr2:179435006;179435005;179435004
N2B	16220	48883;48884;48885	chr2:178570279;178570278;178570277	chr2:179435006;179435005;179435004
Novex-1	16345	49258;49259;49260	chr2:178570279;178570278;178570277	chr2:179435006;179435005;179435004
Novex-2	16412	49459;49460;49461	chr2:178570279;178570278;178570277	chr2:179435006;179435005;179435004
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-71
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.5631
• 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
Y/C	None	None	0.999	N	0.697	0.33	0.460264052551	gnomAD-4.0.0	1.59214E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85935E-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
Y/A	0.9123	likely_pathogenic	0.9081	pathogenic	-0.841	Destabilizing	0.916	D	0.648	neutral	None	None	None	None	I
Y/C	0.4944	ambiguous	0.4923	ambiguous	0.043	Stabilizing	0.999	D	0.697	prob.neutral	N	0.468393043	None	None	I
Y/D	0.885	likely_pathogenic	0.8699	pathogenic	0.878	Stabilizing	0.994	D	0.689	prob.neutral	N	0.500749985	None	None	I
Y/E	0.966	likely_pathogenic	0.9588	pathogenic	0.866	Stabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	I
Y/F	0.1104	likely_benign	0.107	benign	-0.43	Destabilizing	0.892	D	0.538	neutral	N	0.477229612	None	None	I
Y/G	0.9129	likely_pathogenic	0.9125	pathogenic	-1.042	Destabilizing	0.987	D	0.679	prob.neutral	None	None	None	None	I
Y/H	0.532	ambiguous	0.4743	ambiguous	0.118	Stabilizing	0.994	D	0.604	neutral	N	0.474367298	None	None	I
Y/I	0.7554	likely_pathogenic	0.7429	pathogenic	-0.327	Destabilizing	0.073	N	0.478	neutral	None	None	None	None	I
Y/K	0.9561	likely_pathogenic	0.9518	pathogenic	0.133	Stabilizing	0.987	D	0.679	prob.neutral	None	None	None	None	I
Y/L	0.8056	likely_pathogenic	0.798	pathogenic	-0.327	Destabilizing	0.437	N	0.595	neutral	None	None	None	None	I
Y/M	0.8392	likely_pathogenic	0.8211	pathogenic	-0.144	Destabilizing	0.993	D	0.626	neutral	None	None	None	None	I
Y/N	0.6204	likely_pathogenic	0.5779	pathogenic	-0.04	Destabilizing	0.994	D	0.687	prob.neutral	N	0.470555409	None	None	I
Y/P	0.9923	likely_pathogenic	0.9937	pathogenic	-0.48	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	I
Y/Q	0.9228	likely_pathogenic	0.9079	pathogenic	-0.009	Destabilizing	0.996	D	0.647	neutral	None	None	None	None	I
Y/R	0.8984	likely_pathogenic	0.8971	pathogenic	0.431	Stabilizing	0.996	D	0.689	prob.neutral	None	None	None	None	I
Y/S	0.8023	likely_pathogenic	0.7772	pathogenic	-0.515	Destabilizing	0.983	D	0.662	neutral	N	0.469670037	None	None	I
Y/T	0.907	likely_pathogenic	0.9034	pathogenic	-0.434	Destabilizing	0.975	D	0.647	neutral	None	None	None	None	I
Y/V	0.6796	likely_pathogenic	0.6761	pathogenic	-0.48	Destabilizing	0.653	D	0.587	neutral	None	None	None	None	I
Y/W	0.5881	likely_pathogenic	0.5706	pathogenic	-0.491	Destabilizing	0.999	D	0.594	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.