TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33384	100375;100376;100377	chr2:178536959;178536958;178536957	chr2:179401686;179401685;179401684
N2AB	31743	95452;95453;95454	chr2:178536959;178536958;178536957	chr2:179401686;179401685;179401684
N2A	30816	92671;92672;92673	chr2:178536959;178536958;178536957	chr2:179401686;179401685;179401684
N2B	24319	73180;73181;73182	chr2:178536959;178536958;178536957	chr2:179401686;179401685;179401684
Novex-1	24444	73555;73556;73557	chr2:178536959;178536958;178536957	chr2:179401686;179401685;179401684
Novex-2	24511	73756;73757;73758	chr2:178536959;178536958;178536957	chr2:179401686;179401685;179401684
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: 95
• Structural Position: 127
• Q(SASA): 0.2052
• 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
V/M	None	None	0.999	N	0.731	0.13	0.46017455471	gnomAD-4.0.0	2.05431E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.70003E-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
V/A	0.4699	ambiguous	0.4551	ambiguous	-1.073	Destabilizing	0.996	D	0.529	neutral	N	0.50508543	None	None	I
V/C	0.8405	likely_pathogenic	0.8218	pathogenic	-0.535	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
V/D	0.9154	likely_pathogenic	0.9211	pathogenic	-1.211	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	I
V/E	0.7853	likely_pathogenic	0.8065	pathogenic	-0.975	Destabilizing	1.0	D	0.883	deleterious	N	0.489189416	None	None	I
V/F	0.3617	ambiguous	0.3449	ambiguous	-0.533	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	I
V/G	0.6952	likely_pathogenic	0.7001	pathogenic	-1.563	Destabilizing	1.0	D	0.915	deleterious	N	0.489696395	None	None	I
V/H	0.8792	likely_pathogenic	0.8932	pathogenic	-1.275	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	I
V/I	0.0953	likely_benign	0.0879	benign	0.284	Stabilizing	0.668	D	0.229	neutral	None	None	None	None	I
V/K	0.7859	likely_pathogenic	0.8176	pathogenic	-0.711	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
V/L	0.3054	likely_benign	0.2834	benign	0.284	Stabilizing	0.959	D	0.588	neutral	N	0.51049125	None	None	I
V/M	0.2824	likely_benign	0.2395	benign	0.153	Stabilizing	0.999	D	0.731	deleterious	N	0.500661045	None	None	I
V/N	0.7907	likely_pathogenic	0.7938	pathogenic	-1.202	Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	I
V/P	0.9612	likely_pathogenic	0.9659	pathogenic	-0.142	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	I
V/Q	0.7217	likely_pathogenic	0.7567	pathogenic	-0.908	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	I
V/R	0.7513	likely_pathogenic	0.7939	pathogenic	-0.883	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	I
V/S	0.6506	likely_pathogenic	0.6494	pathogenic	-1.773	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	I
V/T	0.4191	ambiguous	0.413	ambiguous	-1.377	Destabilizing	0.997	D	0.581	neutral	None	None	None	None	I
V/W	0.9528	likely_pathogenic	0.9506	pathogenic	-0.98	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	I
V/Y	0.8197	likely_pathogenic	0.8191	pathogenic	-0.5	Destabilizing	1.0	D	0.832	deleterious	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.