TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6816	20671;20672;20673	chr2:178725876;178725875;178725874	chr2:179590603;179590602;179590601
N2AB	6499	19720;19721;19722	chr2:178725876;178725875;178725874	chr2:179590603;179590602;179590601
N2A	5572	16939;16940;16941	chr2:178725876;178725875;178725874	chr2:179590603;179590602;179590601
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-52
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1631
• 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
T/K	rs1203777125	None	0.915	N	0.783	0.31	0.344017737713	gnomAD-4.0.0	4.77777E-06	None	None	None	None	N	None	0	0	None	0	8.32501E-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
T/A	0.0533	likely_benign	0.0497	benign	-0.919	Destabilizing	None	N	0.349	neutral	N	0.429969675	None	None	N
T/C	0.2993	likely_benign	0.2903	benign	-0.662	Destabilizing	0.964	D	0.764	deleterious	None	None	None	None	N
T/D	0.7895	likely_pathogenic	0.7211	pathogenic	-1.76	Destabilizing	0.753	D	0.776	deleterious	None	None	None	None	N
T/E	0.7626	likely_pathogenic	0.7122	pathogenic	-1.549	Destabilizing	0.91	D	0.785	deleterious	None	None	None	None	N
T/F	0.4738	ambiguous	0.4343	ambiguous	-0.577	Destabilizing	0.99	D	0.777	deleterious	None	None	None	None	N
T/G	0.2352	likely_benign	0.2006	benign	-1.348	Destabilizing	0.651	D	0.731	prob.delet.	None	None	None	None	N
T/H	0.488	ambiguous	0.4811	ambiguous	-1.596	Destabilizing	0.974	D	0.745	deleterious	None	None	None	None	N
T/I	0.2842	likely_benign	0.2408	benign	0.21	Stabilizing	0.439	N	0.715	prob.delet.	D	0.524536061	None	None	N
T/K	0.6873	likely_pathogenic	0.6683	pathogenic	-0.423	Destabilizing	0.915	D	0.783	deleterious	N	0.492327642	None	None	N
T/L	0.1843	likely_benign	0.1747	benign	0.21	Stabilizing	0.509	D	0.675	neutral	None	None	None	None	N
T/M	0.1545	likely_benign	0.1471	benign	0.265	Stabilizing	0.973	D	0.769	deleterious	None	None	None	None	N
T/N	0.3072	likely_benign	0.2627	benign	-1.271	Destabilizing	0.861	D	0.753	deleterious	None	None	None	None	N
T/P	0.6246	likely_pathogenic	0.5993	pathogenic	-0.135	Destabilizing	0.069	N	0.775	deleterious	N	0.517071371	None	None	N
T/Q	0.5685	likely_pathogenic	0.5373	ambiguous	-0.97	Destabilizing	0.979	D	0.797	deleterious	None	None	None	None	N
T/R	0.5618	ambiguous	0.5567	ambiguous	-0.765	Destabilizing	0.99	D	0.79	deleterious	N	0.492039641	None	None	N
T/S	0.117	likely_benign	0.1033	benign	-1.389	Destabilizing	0.013	N	0.561	neutral	N	0.464178249	None	None	N
T/V	0.162	likely_benign	0.1369	benign	-0.135	Destabilizing	0.02	N	0.45	neutral	None	None	None	None	N
T/W	0.8442	likely_pathogenic	0.8298	pathogenic	-0.872	Destabilizing	0.996	D	0.747	deleterious	None	None	None	None	N
T/Y	0.4663	ambiguous	0.4438	ambiguous	-0.449	Destabilizing	0.898	D	0.771	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.