TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26294	79105;79106;79107	chr2:178567252;178567251;178567250	chr2:179431979;179431978;179431977
N2AB	24653	74182;74183;74184	chr2:178567252;178567251;178567250	chr2:179431979;179431978;179431977
N2A	23726	71401;71402;71403	chr2:178567252;178567251;178567250	chr2:179431979;179431978;179431977
N2B	17229	51910;51911;51912	chr2:178567252;178567251;178567250	chr2:179431979;179431978;179431977
Novex-1	17354	52285;52286;52287	chr2:178567252;178567251;178567250	chr2:179431979;179431978;179431977
Novex-2	17421	52486;52487;52488	chr2:178567252;178567251;178567250	chr2:179431979;179431978;179431977
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: Fn3-79
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.0962
• 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	0.003	N	0.255	0.061	0.185906805712	gnomAD-4.0.0	1.61007E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46165E-05	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	0.6572	likely_pathogenic	0.5619	ambiguous	-1.646	Destabilizing	0.296	N	0.752	deleterious	N	0.488973423	None	None	N
V/C	0.8756	likely_pathogenic	0.8538	pathogenic	-1.392	Destabilizing	0.991	D	0.714	prob.delet.	None	None	None	None	N
V/D	0.9941	likely_pathogenic	0.9919	pathogenic	-1.561	Destabilizing	0.879	D	0.83	deleterious	N	0.509799929	None	None	N
V/E	0.9845	likely_pathogenic	0.9791	pathogenic	-1.417	Destabilizing	0.906	D	0.785	deleterious	None	None	None	None	N
V/F	0.5477	ambiguous	0.4899	ambiguous	-0.959	Destabilizing	0.782	D	0.745	deleterious	N	0.482034436	None	None	N
V/G	0.8693	likely_pathogenic	0.8204	pathogenic	-2.115	Highly Destabilizing	0.879	D	0.793	deleterious	N	0.510560398	None	None	N
V/H	0.9926	likely_pathogenic	0.9902	pathogenic	-1.822	Destabilizing	0.991	D	0.813	deleterious	None	None	None	None	N
V/I	0.0736	likely_benign	0.0745	benign	-0.392	Destabilizing	0.003	N	0.255	neutral	N	0.444063975	None	None	N
V/K	0.9898	likely_pathogenic	0.9869	pathogenic	-1.313	Destabilizing	0.906	D	0.78	deleterious	None	None	None	None	N
V/L	0.2073	likely_benign	0.1826	benign	-0.392	Destabilizing	0.001	N	0.277	neutral	N	0.405862585	None	None	N
V/M	0.3573	ambiguous	0.3181	benign	-0.561	Destabilizing	0.826	D	0.737	prob.delet.	None	None	None	None	N
V/N	0.9757	likely_pathogenic	0.9681	pathogenic	-1.392	Destabilizing	0.967	D	0.83	deleterious	None	None	None	None	N
V/P	0.8423	likely_pathogenic	0.8014	pathogenic	-0.777	Destabilizing	0.967	D	0.789	deleterious	None	None	None	None	N
V/Q	0.9808	likely_pathogenic	0.9738	pathogenic	-1.324	Destabilizing	0.967	D	0.789	deleterious	None	None	None	None	N
V/R	0.9822	likely_pathogenic	0.9768	pathogenic	-1.146	Destabilizing	0.906	D	0.829	deleterious	None	None	None	None	N
V/S	0.9025	likely_pathogenic	0.8675	pathogenic	-2.061	Highly Destabilizing	0.906	D	0.773	deleterious	None	None	None	None	N
V/T	0.8219	likely_pathogenic	0.7714	pathogenic	-1.775	Destabilizing	0.575	D	0.773	deleterious	None	None	None	None	N
V/W	0.9866	likely_pathogenic	0.9817	pathogenic	-1.321	Destabilizing	0.991	D	0.791	deleterious	None	None	None	None	N
V/Y	0.957	likely_pathogenic	0.946	pathogenic	-0.94	Destabilizing	0.906	D	0.725	prob.delet.	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.