TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6375	19348;19349;19350	chr2:178728915;178728914;178728913	chr2:179593642;179593641;179593640
N2AB	6058	18397;18398;18399	chr2:178728915;178728914;178728913	chr2:179593642;179593641;179593640
N2A	5131	15616;15617;15618	chr2:178728915;178728914;178728913	chr2:179593642;179593641;179593640
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-47
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.0915
• 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
C/G	None	None	0.98	N	0.787	0.587	0.876617020153	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

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
C/A	0.466	ambiguous	0.4916	ambiguous	-1.817	Destabilizing	0.931	D	0.591	neutral	None	None	None	None	N
C/D	0.8871	likely_pathogenic	0.9015	pathogenic	-0.877	Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
C/E	0.9555	likely_pathogenic	0.9623	pathogenic	-0.695	Destabilizing	0.996	D	0.829	deleterious	None	None	None	None	N
C/F	0.6526	likely_pathogenic	0.6949	pathogenic	-1.043	Destabilizing	0.999	D	0.779	deleterious	N	0.507355437	None	None	N
C/G	0.2421	likely_benign	0.267	benign	-2.164	Highly Destabilizing	0.98	D	0.787	deleterious	N	0.501265824	None	None	N
C/H	0.8621	likely_pathogenic	0.8775	pathogenic	-2.113	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
C/I	0.8003	likely_pathogenic	0.8264	pathogenic	-0.888	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
C/K	0.9773	likely_pathogenic	0.9806	pathogenic	-1.165	Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
C/L	0.7898	likely_pathogenic	0.8184	pathogenic	-0.888	Destabilizing	0.993	D	0.69	prob.neutral	None	None	None	None	N
C/M	0.8495	likely_pathogenic	0.8639	pathogenic	0.219	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
C/N	0.6856	likely_pathogenic	0.7351	pathogenic	-1.49	Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	N
C/P	0.9956	likely_pathogenic	0.9958	pathogenic	-1.175	Destabilizing	0.998	D	0.844	deleterious	None	None	None	None	N
C/Q	0.8889	likely_pathogenic	0.9041	pathogenic	-1.181	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
C/R	0.8836	likely_pathogenic	0.898	pathogenic	-1.249	Destabilizing	0.997	D	0.837	deleterious	N	0.486680288	None	None	N
C/S	0.2261	likely_benign	0.2715	benign	-1.956	Destabilizing	0.659	D	0.54	neutral	N	0.493575649	None	None	N
C/T	0.4762	ambiguous	0.5054	ambiguous	-1.589	Destabilizing	0.971	D	0.713	prob.delet.	None	None	None	None	N
C/V	0.6654	likely_pathogenic	0.7021	pathogenic	-1.175	Destabilizing	0.993	D	0.74	deleterious	None	None	None	None	N
C/W	0.9018	likely_pathogenic	0.9196	pathogenic	-1.221	Destabilizing	1.0	D	0.771	deleterious	N	0.495772095	None	None	N
C/Y	0.7716	likely_pathogenic	0.8026	pathogenic	-1.146	Destabilizing	0.999	D	0.792	deleterious	N	0.499215136	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.