TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27454	82585;82586;82587	chr2:178563772;178563771;178563770	chr2:179428499;179428498;179428497
N2AB	25813	77662;77663;77664	chr2:178563772;178563771;178563770	chr2:179428499;179428498;179428497
N2A	24886	74881;74882;74883	chr2:178563772;178563771;178563770	chr2:179428499;179428498;179428497
N2B	18389	55390;55391;55392	chr2:178563772;178563771;178563770	chr2:179428499;179428498;179428497
Novex-1	18514	55765;55766;55767	chr2:178563772;178563771;178563770	chr2:179428499;179428498;179428497
Novex-2	18581	55966;55967;55968	chr2:178563772;178563771;178563770	chr2:179428499;179428498;179428497
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: Fn3-87
• Domain position: 86
• Structural Position: 119
• 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/K	rs1704595513	None	0.581	N	0.629	0.309	0.293502639404	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85851E-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	0.2897	likely_benign	0.2561	benign	-0.706	Destabilizing	0.581	D	0.712	prob.delet.	N	0.477622982	None	None	N
E/C	0.9142	likely_pathogenic	0.8822	pathogenic	-0.35	Destabilizing	0.993	D	0.761	deleterious	None	None	None	None	N
E/D	0.1561	likely_benign	0.1325	benign	-0.764	Destabilizing	0.004	N	0.256	neutral	N	0.488409398	None	None	N
E/F	0.8433	likely_pathogenic	0.8089	pathogenic	-0.477	Destabilizing	0.993	D	0.776	deleterious	None	None	None	None	N
E/G	0.3639	ambiguous	0.3215	benign	-0.97	Destabilizing	0.83	D	0.753	deleterious	N	0.491763991	None	None	N
E/H	0.7094	likely_pathogenic	0.6473	pathogenic	-0.537	Destabilizing	0.98	D	0.697	prob.neutral	None	None	None	None	N
E/I	0.4549	ambiguous	0.402	ambiguous	-0.016	Destabilizing	0.929	D	0.792	deleterious	None	None	None	None	N
E/K	0.2978	likely_benign	0.2603	benign	-0.413	Destabilizing	0.581	D	0.629	neutral	N	0.517249438	None	None	N
E/L	0.5317	ambiguous	0.4703	ambiguous	-0.016	Destabilizing	0.866	D	0.781	deleterious	None	None	None	None	N
E/M	0.5743	likely_pathogenic	0.5293	ambiguous	0.231	Stabilizing	0.993	D	0.767	deleterious	None	None	None	None	N
E/N	0.4078	ambiguous	0.3374	benign	-0.637	Destabilizing	0.764	D	0.753	deleterious	None	None	None	None	N
E/P	0.571	likely_pathogenic	0.5456	ambiguous	-0.225	Destabilizing	0.929	D	0.805	deleterious	None	None	None	None	N
E/Q	0.2487	likely_benign	0.2185	benign	-0.587	Destabilizing	0.83	D	0.727	prob.delet.	N	0.473268115	None	None	N
E/R	0.4902	ambiguous	0.4295	ambiguous	-0.123	Destabilizing	0.866	D	0.756	deleterious	None	None	None	None	N
E/S	0.3556	ambiguous	0.3003	benign	-0.875	Destabilizing	0.48	N	0.666	neutral	None	None	None	None	N
E/T	0.4383	ambiguous	0.3774	ambiguous	-0.676	Destabilizing	0.866	D	0.776	deleterious	None	None	None	None	N
E/V	0.293	likely_benign	0.2559	benign	-0.225	Destabilizing	0.908	D	0.801	deleterious	N	0.517038794	None	None	N
E/W	0.9611	likely_pathogenic	0.9509	pathogenic	-0.305	Destabilizing	0.993	D	0.765	deleterious	None	None	None	None	N
E/Y	0.7561	likely_pathogenic	0.7017	pathogenic	-0.262	Destabilizing	0.993	D	0.801	deleterious	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.