TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7354	22285;22286;22287	chr2:178722839;178722838;178722837	chr2:179587566;179587565;179587564
N2AB	7037	21334;21335;21336	chr2:178722839;178722838;178722837	chr2:179587566;179587565;179587564
N2A	6110	18553;18554;18555	chr2:178722839;178722838;178722837	chr2:179587566;179587565;179587564
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-58
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2599
• 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/A	rs1191619826	None	0.78	D	0.706	0.663	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs1191619826	None	0.78	D	0.706	0.663	None	gnomAD-4.0.0	6.57531E-06	None	None	None	None	I	None	2.41394E-05	0	None	0	0	None	0	0	0	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	0.5779	likely_pathogenic	0.7401	pathogenic	-1.629	Destabilizing	0.78	D	0.706	prob.neutral	D	0.575014259	None	None	I
V/C	0.9243	likely_pathogenic	0.9553	pathogenic	-1.106	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	I
V/D	0.9779	likely_pathogenic	0.9924	pathogenic	-1.399	Destabilizing	0.988	D	0.859	deleterious	None	None	None	None	I
V/E	0.9506	likely_pathogenic	0.979	pathogenic	-1.301	Destabilizing	0.984	D	0.825	deleterious	D	0.613401789	None	None	I
V/F	0.4607	ambiguous	0.6059	pathogenic	-1.025	Destabilizing	0.976	D	0.795	deleterious	None	None	None	None	I
V/G	0.8072	likely_pathogenic	0.9032	pathogenic	-2.06	Highly Destabilizing	0.984	D	0.823	deleterious	D	0.613401789	None	None	I
V/H	0.9788	likely_pathogenic	0.9905	pathogenic	-1.643	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	I
V/I	0.0844	likely_benign	0.09	benign	-0.497	Destabilizing	0.015	N	0.253	neutral	None	None	None	None	I
V/K	0.9648	likely_pathogenic	0.9819	pathogenic	-1.286	Destabilizing	0.988	D	0.833	deleterious	None	None	None	None	I
V/L	0.4365	ambiguous	0.5408	ambiguous	-0.497	Destabilizing	0.64	D	0.523	neutral	D	0.573770939	None	None	I
V/M	0.379	ambiguous	0.4945	ambiguous	-0.439	Destabilizing	0.968	D	0.701	prob.neutral	D	0.561921957	None	None	I
V/N	0.939	likely_pathogenic	0.9746	pathogenic	-1.225	Destabilizing	0.988	D	0.869	deleterious	None	None	None	None	I
V/P	0.9463	likely_pathogenic	0.9705	pathogenic	-0.841	Destabilizing	0.996	D	0.869	deleterious	None	None	None	None	I
V/Q	0.9514	likely_pathogenic	0.9751	pathogenic	-1.238	Destabilizing	0.996	D	0.862	deleterious	None	None	None	None	I
V/R	0.9449	likely_pathogenic	0.9696	pathogenic	-0.963	Destabilizing	0.988	D	0.864	deleterious	None	None	None	None	I
V/S	0.8135	likely_pathogenic	0.9087	pathogenic	-1.867	Destabilizing	0.851	D	0.828	deleterious	None	None	None	None	I
V/T	0.682	likely_pathogenic	0.7859	pathogenic	-1.635	Destabilizing	0.132	N	0.408	neutral	None	None	None	None	I
V/W	0.9792	likely_pathogenic	0.9911	pathogenic	-1.338	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	I
V/Y	0.9121	likely_pathogenic	0.9556	pathogenic	-0.99	Destabilizing	0.996	D	0.781	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.