TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10023	30292;30293;30294	chr2:178704303;178704302;178704301	chr2:179569030;179569029;179569028
N2AB	9706	29341;29342;29343	chr2:178704303;178704302;178704301	chr2:179569030;179569029;179569028
N2A	8779	26560;26561;26562	chr2:178704303;178704302;178704301	chr2:179569030;179569029;179569028
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-85
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.1721
• 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
R/G	None	None	0.722	None	0.669	0.233	0.31501682445	gnomAD-4.0.0	1.36827E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79879E-06	0	0
R/S	None	None	0.565	None	0.625	0.312	0.235664433957	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
R/A	0.8661	likely_pathogenic	0.9458	pathogenic	-1.483	Destabilizing	0.633	D	0.587	neutral	None	None	None	None	N
R/C	0.4423	ambiguous	0.5525	ambiguous	-1.321	Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	N
R/D	0.9874	likely_pathogenic	0.9948	pathogenic	-0.485	Destabilizing	0.923	D	0.702	prob.neutral	None	None	None	None	N
R/E	0.8246	likely_pathogenic	0.9211	pathogenic	-0.308	Destabilizing	0.633	D	0.543	neutral	None	None	None	None	N
R/F	0.8936	likely_pathogenic	0.9451	pathogenic	-1.121	Destabilizing	0.987	D	0.791	deleterious	None	None	None	None	N
R/G	0.8326	likely_pathogenic	0.9352	pathogenic	-1.844	Destabilizing	0.722	D	0.669	neutral	None	None	None	None	N
R/H	0.2947	likely_benign	0.362	ambiguous	-2.087	Highly Destabilizing	0.961	D	0.593	neutral	None	None	None	None	N
R/I	0.5902	likely_pathogenic	0.7479	pathogenic	-0.472	Destabilizing	0.949	D	0.796	deleterious	None	None	None	None	N
R/K	0.1361	likely_benign	0.19	benign	-1.171	Destabilizing	0.003	N	0.181	neutral	None	None	None	None	N
R/L	0.585	likely_pathogenic	0.7005	pathogenic	-0.472	Destabilizing	0.775	D	0.669	neutral	None	None	None	None	N
R/M	0.6507	likely_pathogenic	0.8099	pathogenic	-0.736	Destabilizing	0.996	D	0.703	prob.neutral	None	None	None	None	N
R/N	0.9538	likely_pathogenic	0.9791	pathogenic	-0.869	Destabilizing	0.775	D	0.554	neutral	None	None	None	None	N
R/P	0.991	likely_pathogenic	0.9959	pathogenic	-0.792	Destabilizing	0.961	D	0.748	deleterious	None	None	None	None	N
R/Q	0.2158	likely_benign	0.299	benign	-0.923	Destabilizing	0.633	D	0.553	neutral	None	None	None	None	N
R/S	0.9143	likely_pathogenic	0.9662	pathogenic	-1.772	Destabilizing	0.565	D	0.625	neutral	None	None	None	None	N
R/T	0.8147	likely_pathogenic	0.9268	pathogenic	-1.374	Destabilizing	0.722	D	0.633	neutral	None	None	None	None	N
R/V	0.7233	likely_pathogenic	0.8464	pathogenic	-0.792	Destabilizing	0.923	D	0.752	deleterious	None	None	None	None	N
R/W	0.4934	ambiguous	0.6086	pathogenic	-0.665	Destabilizing	0.996	D	0.774	deleterious	None	None	None	None	N
R/Y	0.808	likely_pathogenic	0.8685	pathogenic	-0.444	Destabilizing	0.987	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.