TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9517	28774;28775;28776	chr2:178709770;178709769;178709768	chr2:179574497;179574496;179574495
N2AB	9200	27823;27824;27825	chr2:178709770;178709769;178709768	chr2:179574497;179574496;179574495
N2A	8273	25042;25043;25044	chr2:178709770;178709769;178709768	chr2:179574497;179574496;179574495
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-81
• Domain position: 25
• Structural Position: 35
• Q(SASA): 0.1385
• 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/A	None	None	0.999	None	0.603	0.596	0.644821044561	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-06	0	0
V/M	None	None	1.0	None	0.758	0.537	0.696542326487	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5685	likely_pathogenic	0.6081	pathogenic	-1.739	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
V/C	0.954	likely_pathogenic	0.9603	pathogenic	-1.585	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/D	0.9968	likely_pathogenic	0.9979	pathogenic	-1.425	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/E	0.9901	likely_pathogenic	0.9927	pathogenic	-1.192	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/F	0.7194	likely_pathogenic	0.7827	pathogenic	-0.988	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
V/G	0.8276	likely_pathogenic	0.8608	pathogenic	-2.298	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/H	0.9966	likely_pathogenic	0.9974	pathogenic	-2.001	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.148	likely_benign	0.1584	benign	-0.183	Destabilizing	0.998	D	0.537	neutral	None	None	None	None	N
V/K	0.995	likely_pathogenic	0.9963	pathogenic	-1.153	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/L	0.6536	likely_pathogenic	0.7286	pathogenic	-0.183	Destabilizing	0.997	D	0.621	neutral	None	None	None	None	N
V/M	0.6755	likely_pathogenic	0.742	pathogenic	-0.48	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
V/N	0.9911	likely_pathogenic	0.9938	pathogenic	-1.441	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/P	0.987	likely_pathogenic	0.9893	pathogenic	-0.673	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/Q	0.9901	likely_pathogenic	0.9925	pathogenic	-1.207	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/R	0.9882	likely_pathogenic	0.9908	pathogenic	-1.22	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/S	0.9175	likely_pathogenic	0.9337	pathogenic	-2.25	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/T	0.7747	likely_pathogenic	0.7857	pathogenic	-1.843	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
V/W	0.9958	likely_pathogenic	0.9972	pathogenic	-1.347	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/Y	0.9796	likely_pathogenic	0.9862	pathogenic	-0.961	Destabilizing	1.0	D	0.845	deleterious	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.