TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21769	65530;65531;65532	chr2:178583877;178583876;178583875	chr2:179448604;179448603;179448602
N2AB	20128	60607;60608;60609	chr2:178583877;178583876;178583875	chr2:179448604;179448603;179448602
N2A	19201	57826;57827;57828	chr2:178583877;178583876;178583875	chr2:179448604;179448603;179448602
N2B	12704	38335;38336;38337	chr2:178583877;178583876;178583875	chr2:179448604;179448603;179448602
Novex-1	12829	38710;38711;38712	chr2:178583877;178583876;178583875	chr2:179448604;179448603;179448602
Novex-2	12896	38911;38912;38913	chr2:178583877;178583876;178583875	chr2:179448604;179448603;179448602
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: Fn3-46
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2101
• 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	rs1426502571	-0.749	0.004	N	0.241	0.078	0.364926071151	gnomAD-2.1.1	4.35E-06	None	None	None	None	N	None	0	0	None	0	5.93E-05	None	0	None	0	0	0
V/I	rs1426502571	-0.749	0.004	N	0.241	0.078	0.364926071151	gnomAD-4.0.0	1.64784E-06	None	None	None	None	N	None	0	0	None	0	2.83094E-05	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	0.4264	ambiguous	0.3814	ambiguous	-1.418	Destabilizing	0.581	D	0.473	neutral	N	0.516001431	None	None	N
V/C	0.8179	likely_pathogenic	0.7887	pathogenic	-1.472	Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
V/D	0.8738	likely_pathogenic	0.8507	pathogenic	-1.292	Destabilizing	0.908	D	0.868	deleterious	N	0.509911607	None	None	N
V/E	0.7275	likely_pathogenic	0.6809	pathogenic	-1.29	Destabilizing	0.929	D	0.833	deleterious	None	None	None	None	N
V/F	0.4756	ambiguous	0.4099	ambiguous	-1.289	Destabilizing	0.83	D	0.796	deleterious	N	0.484681008	None	None	N
V/G	0.6118	likely_pathogenic	0.6051	pathogenic	-1.707	Destabilizing	0.908	D	0.845	deleterious	N	0.48804837	None	None	N
V/H	0.8731	likely_pathogenic	0.8404	pathogenic	-1.258	Destabilizing	0.993	D	0.856	deleterious	None	None	None	None	N
V/I	0.08	likely_benign	0.0657	benign	-0.726	Destabilizing	0.004	N	0.241	neutral	N	0.469399563	None	None	N
V/K	0.5785	likely_pathogenic	0.5568	ambiguous	-1.007	Destabilizing	0.929	D	0.837	deleterious	None	None	None	None	N
V/L	0.4891	ambiguous	0.3962	ambiguous	-0.726	Destabilizing	0.09	N	0.358	neutral	N	0.469459908	None	None	N
V/M	0.2666	likely_benign	0.2201	benign	-0.824	Destabilizing	0.866	D	0.7	prob.neutral	None	None	None	None	N
V/N	0.7196	likely_pathogenic	0.638	pathogenic	-0.91	Destabilizing	0.976	D	0.866	deleterious	None	None	None	None	N
V/P	0.9795	likely_pathogenic	0.979	pathogenic	-0.923	Destabilizing	0.976	D	0.859	deleterious	None	None	None	None	N
V/Q	0.6317	likely_pathogenic	0.5917	pathogenic	-1.11	Destabilizing	0.976	D	0.851	deleterious	None	None	None	None	N
V/R	0.5317	ambiguous	0.5103	ambiguous	-0.602	Destabilizing	0.929	D	0.865	deleterious	None	None	None	None	N
V/S	0.5481	ambiguous	0.4951	ambiguous	-1.474	Destabilizing	0.929	D	0.826	deleterious	None	None	None	None	N
V/T	0.3491	ambiguous	0.2882	benign	-1.358	Destabilizing	0.648	D	0.58	neutral	None	None	None	None	N
V/W	0.9561	likely_pathogenic	0.9499	pathogenic	-1.403	Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	N
V/Y	0.827	likely_pathogenic	0.7905	pathogenic	-1.066	Destabilizing	0.929	D	0.809	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.