TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33380	100363;100364;100365	chr2:178536971;178536970;178536969	chr2:179401698;179401697;179401696
N2AB	31739	95440;95441;95442	chr2:178536971;178536970;178536969	chr2:179401698;179401697;179401696
N2A	30812	92659;92660;92661	chr2:178536971;178536970;178536969	chr2:179401698;179401697;179401696
N2B	24315	73168;73169;73170	chr2:178536971;178536970;178536969	chr2:179401698;179401697;179401696
Novex-1	24440	73543;73544;73545	chr2:178536971;178536970;178536969	chr2:179401698;179401697;179401696
Novex-2	24507	73744;73745;73746	chr2:178536971;178536970;178536969	chr2:179401698;179401697;179401696
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-130
• Domain position: 91
• Structural Position: 123
• Q(SASA): 0.1586
• 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
V/E	rs1461056252	-1.019	0.966	N	0.713	0.36	0.698509492642	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/E	rs1461056252	-1.019	0.966	N	0.713	0.36	0.698509492642	gnomAD-4.0.0	7.96435E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.43032E-05	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
V/A	0.3227	likely_benign	0.2574	benign	-1.092	Destabilizing	0.622	D	0.718	prob.delet.	N	0.420757467	None	None	N
V/C	0.8263	likely_pathogenic	0.7796	pathogenic	-0.788	Destabilizing	0.998	D	0.687	prob.delet.	None	None	None	None	N
V/D	0.644	likely_pathogenic	0.5719	pathogenic	-0.373	Destabilizing	0.974	D	0.805	deleterious	None	None	None	None	N
V/E	0.653	likely_pathogenic	0.5921	pathogenic	-0.263	Destabilizing	0.966	D	0.713	prob.delet.	N	0.427491438	None	None	N
V/F	0.3328	likely_benign	0.2605	benign	-0.495	Destabilizing	0.949	D	0.751	deleterious	None	None	None	None	N
V/G	0.3227	likely_benign	0.2935	benign	-1.51	Destabilizing	0.966	D	0.767	deleterious	N	0.469108774	None	None	N
V/H	0.8561	likely_pathogenic	0.8189	pathogenic	-1.077	Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
V/I	0.0941	likely_benign	0.0839	benign	-0.012	Destabilizing	0.007	N	0.139	neutral	None	None	None	None	N
V/K	0.7661	likely_pathogenic	0.7352	pathogenic	-0.713	Destabilizing	0.974	D	0.725	deleterious	None	None	None	None	N
V/L	0.2998	likely_benign	0.2434	benign	-0.012	Destabilizing	0.264	N	0.493	neutral	N	0.424355132	None	None	N
V/M	0.2714	likely_benign	0.2007	benign	-0.198	Destabilizing	0.933	D	0.684	prob.delet.	N	0.468762057	None	None	N
V/N	0.4448	ambiguous	0.4041	ambiguous	-0.725	Destabilizing	0.974	D	0.813	deleterious	None	None	None	None	N
V/P	0.8637	likely_pathogenic	0.8212	pathogenic	-0.337	Destabilizing	0.991	D	0.772	deleterious	None	None	None	None	N
V/Q	0.7036	likely_pathogenic	0.6638	pathogenic	-0.653	Destabilizing	0.991	D	0.763	deleterious	None	None	None	None	N
V/R	0.7445	likely_pathogenic	0.7146	pathogenic	-0.584	Destabilizing	0.974	D	0.825	deleterious	None	None	None	None	N
V/S	0.3308	likely_benign	0.2907	benign	-1.417	Destabilizing	0.725	D	0.763	deleterious	None	None	None	None	N
V/T	0.2434	likely_benign	0.211	benign	-1.163	Destabilizing	0.066	N	0.411	neutral	None	None	None	None	N
V/W	0.9448	likely_pathogenic	0.9185	pathogenic	-0.787	Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
V/Y	0.7688	likely_pathogenic	0.7096	pathogenic	-0.391	Destabilizing	0.991	D	0.685	prob.delet.	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.