TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5199	15820;15821;15822	chr2:178733794;178733793;178733792	chr2:179598521;179598520;179598519
N2AB	4882	14869;14870;14871	chr2:178733794;178733793;178733792	chr2:179598521;179598520;179598519
N2A	3955	12088;12089;12090	chr2:178733794;178733793;178733792	chr2:179598521;179598520;179598519
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-35
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2559
• 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	rs1370452174	None	1.0	D	0.801	0.623	0.904687970766	gnomAD-4.0.0	7.20193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.87501E-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	0.5223	ambiguous	0.6134	pathogenic	-1.494	Destabilizing	0.999	D	0.638	neutral	D	0.731423794	None	None	N
V/C	0.8738	likely_pathogenic	0.9137	pathogenic	-0.914	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/D	0.9703	likely_pathogenic	0.9831	pathogenic	-1.272	Destabilizing	1.0	D	0.859	deleterious	D	0.822675105	None	None	N
V/E	0.927	likely_pathogenic	0.9547	pathogenic	-1.168	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/F	0.3604	ambiguous	0.4143	ambiguous	-0.911	Destabilizing	1.0	D	0.801	deleterious	D	0.654161015	None	None	N
V/G	0.7508	likely_pathogenic	0.8188	pathogenic	-1.916	Destabilizing	1.0	D	0.872	deleterious	D	0.822675105	None	None	N
V/H	0.962	likely_pathogenic	0.9776	pathogenic	-1.486	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.076	likely_benign	0.08	benign	-0.391	Destabilizing	0.997	D	0.611	neutral	N	0.497877947	None	None	N
V/K	0.9263	likely_pathogenic	0.9547	pathogenic	-1.153	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/L	0.2551	likely_benign	0.3112	benign	-0.391	Destabilizing	0.997	D	0.659	neutral	D	0.634488515	None	None	N
V/M	0.2432	likely_benign	0.2843	benign	-0.346	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
V/N	0.9045	likely_pathogenic	0.9421	pathogenic	-1.099	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/P	0.9133	likely_pathogenic	0.9443	pathogenic	-0.725	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/Q	0.9084	likely_pathogenic	0.9445	pathogenic	-1.098	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/R	0.9051	likely_pathogenic	0.9388	pathogenic	-0.861	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/S	0.7847	likely_pathogenic	0.8488	pathogenic	-1.712	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/T	0.5455	ambiguous	0.6338	pathogenic	-1.475	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
V/W	0.9597	likely_pathogenic	0.9741	pathogenic	-1.231	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/Y	0.8726	likely_pathogenic	0.912	pathogenic	-0.866	Destabilizing	1.0	D	0.798	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.