TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25624	77095;77096;77097	chr2:178569262;178569261;178569260	chr2:179433989;179433988;179433987
N2AB	23983	72172;72173;72174	chr2:178569262;178569261;178569260	chr2:179433989;179433988;179433987
N2A	23056	69391;69392;69393	chr2:178569262;178569261;178569260	chr2:179433989;179433988;179433987
N2B	16559	49900;49901;49902	chr2:178569262;178569261;178569260	chr2:179433989;179433988;179433987
Novex-1	16684	50275;50276;50277	chr2:178569262;178569261;178569260	chr2:179433989;179433988;179433987
Novex-2	16751	50476;50477;50478	chr2:178569262;178569261;178569260	chr2:179433989;179433988;179433987
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-74
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4341
• 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
P/A	None	None	0.807	N	0.699	0.381	0.240491677333	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
P/L	None	None	0.994	N	0.853	0.451	0.685676517872	gnomAD-4.0.0	1.61278E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8958E-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
P/A	0.0749	likely_benign	0.0793	benign	-1.855	Destabilizing	0.807	D	0.699	prob.neutral	N	0.484025085	None	None	I
P/C	0.5568	ambiguous	0.6122	pathogenic	-1.189	Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	I
P/D	0.7051	likely_pathogenic	0.7311	pathogenic	-2.231	Highly Destabilizing	0.825	D	0.837	deleterious	None	None	None	None	I
P/E	0.4497	ambiguous	0.4756	ambiguous	-2.111	Highly Destabilizing	0.882	D	0.781	deleterious	None	None	None	None	I
P/F	0.5598	ambiguous	0.6056	pathogenic	-1.267	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	I
P/G	0.4394	ambiguous	0.4617	ambiguous	-2.266	Highly Destabilizing	0.98	D	0.785	deleterious	None	None	None	None	I
P/H	0.3288	likely_benign	0.3619	ambiguous	-1.797	Destabilizing	0.242	N	0.43	neutral	D	0.52325983	None	None	I
P/I	0.2568	likely_benign	0.2794	benign	-0.759	Destabilizing	0.998	D	0.884	deleterious	None	None	None	None	I
P/K	0.4913	ambiguous	0.5272	ambiguous	-1.702	Destabilizing	0.996	D	0.831	deleterious	None	None	None	None	I
P/L	0.1087	likely_benign	0.1184	benign	-0.759	Destabilizing	0.994	D	0.853	deleterious	N	0.494938131	None	None	I
P/M	0.2123	likely_benign	0.2211	benign	-0.59	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
P/N	0.3966	ambiguous	0.4283	ambiguous	-1.738	Destabilizing	0.937	D	0.862	deleterious	None	None	None	None	I
P/Q	0.2134	likely_benign	0.2282	benign	-1.762	Destabilizing	0.989	D	0.869	deleterious	None	None	None	None	I
P/R	0.4238	ambiguous	0.4653	ambiguous	-1.271	Destabilizing	0.994	D	0.858	deleterious	N	0.506863868	None	None	I
P/S	0.1613	likely_benign	0.1735	benign	-2.242	Highly Destabilizing	0.98	D	0.773	deleterious	N	0.485049857	None	None	I
P/T	0.1283	likely_benign	0.1387	benign	-2.0	Highly Destabilizing	0.978	D	0.841	deleterious	N	0.501432592	None	None	I
P/V	0.1792	likely_benign	0.1935	benign	-1.095	Destabilizing	0.988	D	0.856	deleterious	None	None	None	None	I
P/W	0.835	likely_pathogenic	0.8602	pathogenic	-1.619	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
P/Y	0.5723	likely_pathogenic	0.6116	pathogenic	-1.277	Destabilizing	0.992	D	0.886	deleterious	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.