TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32914	98965;98966;98967	chr2:178539195;178539194;178539193	chr2:179403922;179403921;179403920
N2AB	31273	94042;94043;94044	chr2:178539195;178539194;178539193	chr2:179403922;179403921;179403920
N2A	30346	91261;91262;91263	chr2:178539195;178539194;178539193	chr2:179403922;179403921;179403920
N2B	23849	71770;71771;71772	chr2:178539195;178539194;178539193	chr2:179403922;179403921;179403920
Novex-1	23974	72145;72146;72147	chr2:178539195;178539194;178539193	chr2:179403922;179403921;179403920
Novex-2	24041	72346;72347;72348	chr2:178539195;178539194;178539193	chr2:179403922;179403921;179403920
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-128
• Domain position: 19
• Structural Position: 20
• Q(SASA): 0.1163
• 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/L	None	None	0.247	N	0.486	0.068	0.21737058555	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.5814	likely_pathogenic	0.5071	ambiguous	-2.303	Highly Destabilizing	0.822	D	0.575	neutral	N	0.491700419	None	None	N
V/C	0.9104	likely_pathogenic	0.8456	pathogenic	-2.535	Highly Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
V/D	0.9987	likely_pathogenic	0.9989	pathogenic	-2.793	Highly Destabilizing	0.99	D	0.859	deleterious	D	0.533500045	None	None	N
V/E	0.9948	likely_pathogenic	0.9957	pathogenic	-2.549	Highly Destabilizing	0.993	D	0.864	deleterious	None	None	None	None	N
V/F	0.7788	likely_pathogenic	0.8191	pathogenic	-1.548	Destabilizing	0.942	D	0.866	deleterious	N	0.505734551	None	None	N
V/G	0.9173	likely_pathogenic	0.9139	pathogenic	-2.873	Highly Destabilizing	0.971	D	0.858	deleterious	D	0.533246555	None	None	N
V/H	0.9977	likely_pathogenic	0.9977	pathogenic	-2.61	Highly Destabilizing	0.998	D	0.856	deleterious	None	None	None	None	N
V/I	0.0991	likely_benign	0.0977	benign	-0.696	Destabilizing	0.014	N	0.207	neutral	N	0.465644394	None	None	N
V/K	0.9958	likely_pathogenic	0.997	pathogenic	-1.964	Destabilizing	0.978	D	0.863	deleterious	None	None	None	None	N
V/L	0.4797	ambiguous	0.4892	ambiguous	-0.696	Destabilizing	0.247	N	0.486	neutral	N	0.510744753	None	None	N
V/M	0.4906	ambiguous	0.5334	ambiguous	-1.087	Destabilizing	0.956	D	0.743	deleterious	None	None	None	None	N
V/N	0.9934	likely_pathogenic	0.9923	pathogenic	-2.412	Highly Destabilizing	0.993	D	0.879	deleterious	None	None	None	None	N
V/P	0.9985	likely_pathogenic	0.9985	pathogenic	-1.206	Destabilizing	0.993	D	0.872	deleterious	None	None	None	None	N
V/Q	0.9905	likely_pathogenic	0.9916	pathogenic	-2.207	Highly Destabilizing	0.993	D	0.881	deleterious	None	None	None	None	N
V/R	0.99	likely_pathogenic	0.9922	pathogenic	-1.855	Destabilizing	0.993	D	0.879	deleterious	None	None	None	None	N
V/S	0.9376	likely_pathogenic	0.9154	pathogenic	-3.129	Highly Destabilizing	0.978	D	0.853	deleterious	None	None	None	None	N
V/T	0.8465	likely_pathogenic	0.8135	pathogenic	-2.714	Highly Destabilizing	0.86	D	0.677	prob.neutral	None	None	None	None	N
V/W	0.9983	likely_pathogenic	0.9984	pathogenic	-1.956	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
V/Y	0.9865	likely_pathogenic	0.9878	pathogenic	-1.614	Destabilizing	0.978	D	0.861	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.