TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7835	23728;23729;23730	chr2:178720139;178720138;178720137	chr2:179584866;179584865;179584864
N2AB	7518	22777;22778;22779	chr2:178720139;178720138;178720137	chr2:179584866;179584865;179584864
N2A	6591	19996;19997;19998	chr2:178720139;178720138;178720137	chr2:179584866;179584865;179584864
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-63
• Domain position: 41
• Structural Position: 57
• Q(SASA): 0.3466
• 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/F	None	None	0.901	N	0.471	0.287	0.695974831096	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
V/I	rs757420766	-0.348	0.003	N	0.184	0.061	0.260735089382	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
V/I	rs757420766	-0.348	0.003	N	0.184	0.061	0.260735089382	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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	0.3525	ambiguous	0.2274	benign	-0.907	Destabilizing	0.349	N	0.4	neutral	N	0.510430614	None	None	N
V/C	0.894	likely_pathogenic	0.8185	pathogenic	-0.76	Destabilizing	0.996	D	0.505	neutral	None	None	None	None	N
V/D	0.5355	ambiguous	0.3422	ambiguous	-0.672	Destabilizing	0.901	D	0.559	neutral	N	0.484234298	None	None	N
V/E	0.4231	ambiguous	0.2607	benign	-0.731	Destabilizing	0.923	D	0.493	neutral	None	None	None	None	N
V/F	0.2083	likely_benign	0.1571	benign	-0.786	Destabilizing	0.901	D	0.471	neutral	N	0.499050551	None	None	N
V/G	0.3983	ambiguous	0.2593	benign	-1.126	Destabilizing	0.901	D	0.491	neutral	N	0.505126938	None	None	N
V/H	0.7758	likely_pathogenic	0.6331	pathogenic	-0.598	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	N
V/I	0.0669	likely_benign	0.0681	benign	-0.446	Destabilizing	0.003	N	0.184	neutral	N	0.417984599	None	None	N
V/K	0.6329	likely_pathogenic	0.4496	ambiguous	-0.883	Destabilizing	0.923	D	0.504	neutral	None	None	None	None	N
V/L	0.2154	likely_benign	0.1708	benign	-0.446	Destabilizing	0.075	N	0.272	neutral	N	0.452942535	None	None	N
V/M	0.1671	likely_benign	0.1322	benign	-0.468	Destabilizing	0.923	D	0.475	neutral	None	None	None	None	N
V/N	0.4247	ambiguous	0.2574	benign	-0.68	Destabilizing	0.923	D	0.571	neutral	None	None	None	None	N
V/P	0.5503	ambiguous	0.3943	ambiguous	-0.564	Destabilizing	0.961	D	0.538	neutral	None	None	None	None	N
V/Q	0.5686	likely_pathogenic	0.3927	ambiguous	-0.88	Destabilizing	0.961	D	0.541	neutral	None	None	None	None	N
V/R	0.597	likely_pathogenic	0.4426	ambiguous	-0.324	Destabilizing	0.923	D	0.575	neutral	None	None	None	None	N
V/S	0.4537	ambiguous	0.2795	benign	-1.089	Destabilizing	0.633	D	0.453	neutral	None	None	None	None	N
V/T	0.377	ambiguous	0.2183	benign	-1.046	Destabilizing	0.011	N	0.221	neutral	None	None	None	None	N
V/W	0.8347	likely_pathogenic	0.7531	pathogenic	-0.912	Destabilizing	0.996	D	0.649	neutral	None	None	None	None	N
V/Y	0.604	likely_pathogenic	0.4865	ambiguous	-0.632	Destabilizing	0.961	D	0.487	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.