TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18029	54310;54311;54312	chr2:178605092;178605091;178605090	chr2:179469819;179469818;179469817
N2AB	16388	49387;49388;49389	chr2:178605092;178605091;178605090	chr2:179469819;179469818;179469817
N2A	15461	46606;46607;46608	chr2:178605092;178605091;178605090	chr2:179469819;179469818;179469817
N2B	8964	27115;27116;27117	chr2:178605092;178605091;178605090	chr2:179469819;179469818;179469817
Novex-1	9089	27490;27491;27492	chr2:178605092;178605091;178605090	chr2:179469819;179469818;179469817
Novex-2	9156	27691;27692;27693	chr2:178605092;178605091;178605090	chr2:179469819;179469818;179469817
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-114
• Domain position: 62
• Structural Position: 137
• Q(SASA): 0.3558
• 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/K	None	None	0.061	N	0.279	0.2	0.223146558224	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1495	likely_benign	0.1544	benign	-0.924	Destabilizing	0.826	D	0.446	neutral	N	0.447440715	None	None	N
E/C	0.7522	likely_pathogenic	0.7547	pathogenic	-0.586	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
E/D	0.219	likely_benign	0.2426	benign	-1.421	Destabilizing	0.959	D	0.515	neutral	N	0.474357957	None	None	N
E/F	0.6348	likely_pathogenic	0.6334	pathogenic	-0.596	Destabilizing	0.997	D	0.637	neutral	None	None	None	None	N
E/G	0.2543	likely_benign	0.2772	benign	-1.339	Destabilizing	0.959	D	0.516	neutral	N	0.445979277	None	None	N
E/H	0.3955	ambiguous	0.3897	ambiguous	-0.971	Destabilizing	0.997	D	0.489	neutral	None	None	None	None	N
E/I	0.2391	likely_benign	0.2338	benign	0.225	Stabilizing	0.982	D	0.617	neutral	None	None	None	None	N
E/K	0.1929	likely_benign	0.1833	benign	-1.039	Destabilizing	0.061	N	0.279	neutral	N	0.39314487	None	None	N
E/L	0.3337	likely_benign	0.3391	benign	0.225	Stabilizing	0.939	D	0.544	neutral	None	None	None	None	N
E/M	0.3483	ambiguous	0.3274	benign	0.832	Stabilizing	0.999	D	0.606	neutral	None	None	None	None	N
E/N	0.2782	likely_benign	0.2895	benign	-1.435	Destabilizing	0.969	D	0.465	neutral	None	None	None	None	N
E/P	0.9869	likely_pathogenic	0.9908	pathogenic	-0.137	Destabilizing	0.997	D	0.502	neutral	None	None	None	None	N
E/Q	0.1264	likely_benign	0.1221	benign	-1.199	Destabilizing	0.92	D	0.481	neutral	N	0.439629308	None	None	N
E/R	0.3093	likely_benign	0.2934	benign	-0.906	Destabilizing	0.884	D	0.45	neutral	None	None	None	None	N
E/S	0.1775	likely_benign	0.1803	benign	-1.899	Destabilizing	0.884	D	0.497	neutral	None	None	None	None	N
E/T	0.1629	likely_benign	0.1631	benign	-1.539	Destabilizing	0.17	N	0.353	neutral	None	None	None	None	N
E/V	0.1559	likely_benign	0.1544	benign	-0.137	Destabilizing	0.92	D	0.519	neutral	N	0.418600675	None	None	N
E/W	0.8869	likely_pathogenic	0.8815	pathogenic	-0.556	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
E/Y	0.5718	likely_pathogenic	0.5603	ambiguous	-0.391	Destabilizing	0.997	D	0.605	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.