TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35608	107047;107048;107049	chr2:178528929;178528928;178528927	chr2:179393656;179393655;179393654
N2AB	33967	102124;102125;102126	chr2:178528929;178528928;178528927	chr2:179393656;179393655;179393654
N2A	33040	99343;99344;99345	chr2:178528929;178528928;178528927	chr2:179393656;179393655;179393654
N2B	26543	79852;79853;79854	chr2:178528929;178528928;178528927	chr2:179393656;179393655;179393654
Novex-1	26668	80227;80228;80229	chr2:178528929;178528928;178528927	chr2:179393656;179393655;179393654
Novex-2	26735	80428;80429;80430	chr2:178528929;178528928;178528927	chr2:179393656;179393655;179393654
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-167
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5871
• 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
E/A	None	None	0.997	N	0.705	0.493	0.46070373	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs766501757	0.232	0.997	N	0.68	0.362	0.40844402	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
E/K	rs766501757	0.232	0.997	N	0.68	0.362	0.40844402	gnomAD-4.0.0	1.5909E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85752E-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	0.2249	likely_benign	0.214	benign	-0.241	Destabilizing	0.997	D	0.705	prob.neutral	N	0.48162785	None	None	I
E/C	0.9623	likely_pathogenic	0.9533	pathogenic	-0.153	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
E/D	0.2206	likely_benign	0.1935	benign	-0.337	Destabilizing	0.997	D	0.545	neutral	N	0.48128113	None	None	I
E/F	0.8723	likely_pathogenic	0.8524	pathogenic	-0.01	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
E/G	0.2424	likely_benign	0.2328	benign	-0.445	Destabilizing	0.999	D	0.701	prob.neutral	N	0.48249465	None	None	I
E/H	0.6715	likely_pathogenic	0.622	pathogenic	0.332	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
E/I	0.5181	ambiguous	0.4945	ambiguous	0.262	Stabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
E/K	0.1776	likely_benign	0.1658	benign	0.352	Stabilizing	0.997	D	0.68	prob.neutral	N	0.4809344	None	None	I
E/L	0.6146	likely_pathogenic	0.5754	pathogenic	0.262	Stabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
E/M	0.6354	likely_pathogenic	0.605	pathogenic	0.183	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
E/N	0.3754	ambiguous	0.3442	ambiguous	-0.059	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	I
E/P	0.7628	likely_pathogenic	0.735	pathogenic	0.115	Stabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
E/Q	0.2014	likely_benign	0.1869	benign	None	Stabilizing	0.999	D	0.639	neutral	N	0.4818012	None	None	I
E/R	0.3571	ambiguous	0.3279	benign	0.623	Stabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	I
E/S	0.3131	likely_benign	0.2885	benign	-0.201	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	I
E/T	0.3328	likely_benign	0.3099	benign	-0.028	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
E/V	0.3063	likely_benign	0.2919	benign	0.115	Stabilizing	0.999	D	0.739	prob.delet.	N	0.4823213	None	None	I
E/W	0.9638	likely_pathogenic	0.9554	pathogenic	0.152	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
E/Y	0.8177	likely_pathogenic	0.7807	pathogenic	0.241	Stabilizing	1.0	D	0.714	prob.delet.	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.