TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20118	60577;60578;60579	chr2:178591373;178591372;178591371	chr2:179456100;179456099;179456098
N2AB	18477	55654;55655;55656	chr2:178591373;178591372;178591371	chr2:179456100;179456099;179456098
N2A	17550	52873;52874;52875	chr2:178591373;178591372;178591371	chr2:179456100;179456099;179456098
N2B	11053	33382;33383;33384	chr2:178591373;178591372;178591371	chr2:179456100;179456099;179456098
Novex-1	11178	33757;33758;33759	chr2:178591373;178591372;178591371	chr2:179456100;179456099;179456098
Novex-2	11245	33958;33959;33960	chr2:178591373;178591372;178591371	chr2:179456100;179456099;179456098
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-120
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.4896
• 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
E/G	None	None	1.0	N	0.671	0.531	0.571137827458	gnomAD-4.0.0	1.59228E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86028E-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
E/A	0.1302	likely_benign	0.1299	benign	-0.417	Destabilizing	0.999	D	0.654	neutral	N	0.510086684	None	None	N
E/C	0.7634	likely_pathogenic	0.7792	pathogenic	-0.116	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/D	0.1078	likely_benign	0.1088	benign	-0.405	Destabilizing	0.999	D	0.474	neutral	N	0.483092084	None	None	N
E/F	0.6041	likely_pathogenic	0.6069	pathogenic	-0.259	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/G	0.1836	likely_benign	0.1857	benign	-0.619	Destabilizing	1.0	D	0.671	neutral	N	0.50290212	None	None	N
E/H	0.4078	ambiguous	0.4103	ambiguous	-0.033	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
E/I	0.1714	likely_benign	0.1708	benign	0.083	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
E/K	0.1501	likely_benign	0.1447	benign	0.26	Stabilizing	0.999	D	0.606	neutral	D	0.5262855	None	None	N
E/L	0.2535	likely_benign	0.2513	benign	0.083	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/M	0.2996	likely_benign	0.2963	benign	0.149	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	N
E/N	0.1914	likely_benign	0.194	benign	-0.094	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/P	0.2918	likely_benign	0.2924	benign	-0.063	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/Q	0.1431	likely_benign	0.1409	benign	-0.052	Destabilizing	1.0	D	0.577	neutral	N	0.515031144	None	None	N
E/R	0.2814	likely_benign	0.2736	benign	0.475	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/S	0.1793	likely_benign	0.1783	benign	-0.241	Destabilizing	0.999	D	0.612	neutral	None	None	None	None	N
E/T	0.1528	likely_benign	0.1529	benign	-0.074	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/V	0.1143	likely_benign	0.1158	benign	-0.063	Destabilizing	1.0	D	0.715	prob.delet.	N	0.483036156	None	None	N
E/W	0.8617	likely_pathogenic	0.863	pathogenic	-0.095	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/Y	0.5304	ambiguous	0.5306	ambiguous	-0.015	Destabilizing	1.0	D	0.679	prob.neutral	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.