TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7377	22354;22355;22356	chr2:178722770;178722769;178722768	chr2:179587497;179587496;179587495
N2AB	7060	21403;21404;21405	chr2:178722770;178722769;178722768	chr2:179587497;179587496;179587495
N2A	6133	18622;18623;18624	chr2:178722770;178722769;178722768	chr2:179587497;179587496;179587495
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: 55
• Structural Position: 135
• Q(SASA): 0.2109
• 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/M	rs1490395674	-0.646	0.06	D	0.435	0.142	0.37479162749	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
V/M	rs1490395674	-0.646	0.06	D	0.435	0.142	0.37479162749	gnomAD-4.0.0	4.77704E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57947E-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	0.2095	likely_benign	0.3286	benign	-1.562	Destabilizing	0.123	N	0.449	neutral	N	0.512489484	None	None	N
V/C	0.8247	likely_pathogenic	0.8751	pathogenic	-1.199	Destabilizing	0.987	D	0.604	neutral	None	None	None	None	N
V/D	0.4432	ambiguous	0.6149	pathogenic	-2.192	Highly Destabilizing	0.94	D	0.742	deleterious	None	None	None	None	N
V/E	0.2834	likely_benign	0.4058	ambiguous	-2.196	Highly Destabilizing	0.658	D	0.681	prob.neutral	N	0.500944339	None	None	N
V/F	0.1815	likely_benign	0.2373	benign	-1.391	Destabilizing	0.854	D	0.631	neutral	None	None	None	None	N
V/G	0.3746	ambiguous	0.5497	ambiguous	-1.87	Destabilizing	0.888	D	0.702	prob.neutral	N	0.479513061	None	None	N
V/H	0.5559	ambiguous	0.6746	pathogenic	-1.509	Destabilizing	0.99	D	0.722	prob.delet.	None	None	None	None	N
V/I	0.067	likely_benign	0.0706	benign	-0.805	Destabilizing	0.002	N	0.154	neutral	None	None	None	None	N
V/K	0.2778	likely_benign	0.3984	ambiguous	-1.273	Destabilizing	0.733	D	0.671	neutral	None	None	None	None	N
V/L	0.2273	likely_benign	0.2937	benign	-0.805	Destabilizing	None	N	0.141	neutral	N	0.504390076	None	None	N
V/M	0.1214	likely_benign	0.1562	benign	-0.586	Destabilizing	0.06	N	0.435	neutral	D	0.533635547	None	None	N
V/N	0.3296	likely_benign	0.4523	ambiguous	-1.183	Destabilizing	0.453	N	0.745	deleterious	None	None	None	None	N
V/P	0.9729	likely_pathogenic	0.9885	pathogenic	-1.025	Destabilizing	0.716	D	0.699	prob.neutral	None	None	None	None	N
V/Q	0.3115	likely_benign	0.4247	ambiguous	-1.409	Destabilizing	0.661	D	0.703	prob.neutral	None	None	None	None	N
V/R	0.2614	likely_benign	0.3689	ambiguous	-0.749	Destabilizing	0.854	D	0.742	deleterious	None	None	None	None	N
V/S	0.275	likely_benign	0.4097	ambiguous	-1.605	Destabilizing	0.76	D	0.639	neutral	None	None	None	None	N
V/T	0.152	likely_benign	0.2064	benign	-1.51	Destabilizing	0.267	N	0.492	neutral	None	None	None	None	N
V/W	0.8067	likely_pathogenic	0.8855	pathogenic	-1.65	Destabilizing	0.997	D	0.734	prob.delet.	None	None	None	None	N
V/Y	0.5315	ambiguous	0.6291	pathogenic	-1.326	Destabilizing	0.922	D	0.64	neutral	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.