TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6230	18913;18914;18915	chr2:178729468;178729467;178729466	chr2:179594195;179594194;179594193
N2AB	5913	17962;17963;17964	chr2:178729468;178729467;178729466	chr2:179594195;179594194;179594193
N2A	4986	15181;15182;15183	chr2:178729468;178729467;178729466	chr2:179594195;179594194;179594193
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-46
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1903
• 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/I	None	None	0.543	N	0.203	0.217	0.532986417303	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	0.3636	ambiguous	0.3589	ambiguous	-1.534	Destabilizing	0.994	D	0.633	neutral	D	0.572692612	None	None	N
V/C	0.8666	likely_pathogenic	0.8761	pathogenic	-0.873	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/D	0.864	likely_pathogenic	0.8471	pathogenic	-1.34	Destabilizing	0.999	D	0.859	deleterious	D	0.624777857	None	None	N
V/E	0.7738	likely_pathogenic	0.7596	pathogenic	-1.277	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/F	0.3443	ambiguous	0.3583	ambiguous	-1.077	Destabilizing	0.998	D	0.803	deleterious	D	0.557864435	None	None	N
V/G	0.3941	ambiguous	0.3893	ambiguous	-1.912	Destabilizing	0.999	D	0.856	deleterious	D	0.624777857	None	None	N
V/H	0.9035	likely_pathogenic	0.9075	pathogenic	-1.457	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/I	0.0934	likely_benign	0.1009	benign	-0.566	Destabilizing	0.543	D	0.203	neutral	N	0.459415508	None	None	N
V/K	0.7574	likely_pathogenic	0.7469	pathogenic	-1.18	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/L	0.4202	ambiguous	0.4554	ambiguous	-0.566	Destabilizing	0.948	D	0.545	neutral	D	0.531842352	None	None	N
V/M	0.2644	likely_benign	0.2763	benign	-0.428	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
V/N	0.7363	likely_pathogenic	0.7398	pathogenic	-1.034	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/P	0.7987	likely_pathogenic	0.8077	pathogenic	-0.855	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/Q	0.7886	likely_pathogenic	0.7843	pathogenic	-1.105	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/R	0.7477	likely_pathogenic	0.7275	pathogenic	-0.784	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/S	0.5905	likely_pathogenic	0.5947	pathogenic	-1.59	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/T	0.4671	ambiguous	0.4518	ambiguous	-1.402	Destabilizing	0.996	D	0.746	deleterious	None	None	None	None	N
V/W	0.9249	likely_pathogenic	0.9271	pathogenic	-1.34	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/Y	0.7541	likely_pathogenic	0.778	pathogenic	-1.01	Destabilizing	1.0	D	0.793	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.