TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33442	100549;100550;100551	chr2:178536423;178536422;178536421	chr2:179401150;179401149;179401148
N2AB	31801	95626;95627;95628	chr2:178536423;178536422;178536421	chr2:179401150;179401149;179401148
N2A	30874	92845;92846;92847	chr2:178536423;178536422;178536421	chr2:179401150;179401149;179401148
N2B	24377	73354;73355;73356	chr2:178536423;178536422;178536421	chr2:179401150;179401149;179401148
Novex-1	24502	73729;73730;73731	chr2:178536423;178536422;178536421	chr2:179401150;179401149;179401148
Novex-2	24569	73930;73931;73932	chr2:178536423;178536422;178536421	chr2:179401150;179401149;179401148
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: Fn3-131
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.1926
• 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	rs1691526659	None	1.0	N	0.713	0.353	0.540427443213	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.4425	ambiguous	0.4352	ambiguous	-1.249	Destabilizing	0.999	D	0.535	neutral	N	0.459606643	None	None	I
V/C	0.8436	likely_pathogenic	0.8304	pathogenic	-1.091	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
V/D	0.9527	likely_pathogenic	0.9701	pathogenic	-0.62	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
V/E	0.8857	likely_pathogenic	0.9169	pathogenic	-0.525	Destabilizing	1.0	D	0.753	deleterious	N	0.504361291	None	None	I
V/F	0.6669	likely_pathogenic	0.7094	pathogenic	-0.733	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
V/G	0.7533	likely_pathogenic	0.7909	pathogenic	-1.629	Destabilizing	1.0	D	0.769	deleterious	N	0.494525922	None	None	I
V/H	0.9746	likely_pathogenic	0.9797	pathogenic	-1.001	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
V/I	0.1145	likely_benign	0.1028	benign	-0.278	Destabilizing	0.998	D	0.456	neutral	None	None	None	None	I
V/K	0.9444	likely_pathogenic	0.9623	pathogenic	-0.938	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
V/L	0.5187	ambiguous	0.5269	ambiguous	-0.278	Destabilizing	0.997	D	0.51	neutral	N	0.497354168	None	None	I
V/M	0.4534	ambiguous	0.4573	ambiguous	-0.492	Destabilizing	1.0	D	0.713	prob.delet.	N	0.483423106	None	None	I
V/N	0.8883	likely_pathogenic	0.9189	pathogenic	-1.03	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
V/P	0.9557	likely_pathogenic	0.9689	pathogenic	-0.568	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
V/Q	0.9052	likely_pathogenic	0.9256	pathogenic	-0.976	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
V/R	0.9245	likely_pathogenic	0.9493	pathogenic	-0.69	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
V/S	0.712	likely_pathogenic	0.7419	pathogenic	-1.668	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
V/T	0.5321	ambiguous	0.5501	ambiguous	-1.424	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	I
V/W	0.9936	likely_pathogenic	0.9948	pathogenic	-0.944	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
V/Y	0.9601	likely_pathogenic	0.9677	pathogenic	-0.597	Destabilizing	1.0	D	0.803	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.