TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5357	16294;16295;16296	chr2:178733107;178733106;178733105	chr2:179597834;179597833;179597832
N2AB	5040	15343;15344;15345	chr2:178733107;178733106;178733105	chr2:179597834;179597833;179597832
N2A	4113	12562;12563;12564	chr2:178733107;178733106;178733105	chr2:179597834;179597833;179597832
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-37
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1434
• 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
P/S	rs1467703602	-1.864	1.0	D	0.882	0.613	0.698733648705	gnomAD-2.1.1	4.26E-06	None	None	None	None	N	None	0	0	None	0	5.63E-05	None	0	None	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
P/A	0.8743	likely_pathogenic	0.8871	pathogenic	-1.703	Destabilizing	0.998	D	0.798	deleterious	D	0.612833866	None	None	N
P/C	0.9946	likely_pathogenic	0.9953	pathogenic	-1.218	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9992	pathogenic	-1.525	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/E	0.9982	likely_pathogenic	0.998	pathogenic	-1.47	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
P/F	0.9993	likely_pathogenic	0.9993	pathogenic	-1.243	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/G	0.9922	likely_pathogenic	0.9924	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/H	0.9974	likely_pathogenic	0.9973	pathogenic	-1.64	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/I	0.9885	likely_pathogenic	0.9885	pathogenic	-0.722	Destabilizing	0.998	D	0.868	deleterious	None	None	None	None	N
P/K	0.999	likely_pathogenic	0.9988	pathogenic	-1.216	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/L	0.9499	likely_pathogenic	0.9579	pathogenic	-0.722	Destabilizing	0.64	D	0.747	deleterious	D	0.625077871	None	None	N
P/M	0.9961	likely_pathogenic	0.9967	pathogenic	-0.615	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/N	0.9986	likely_pathogenic	0.9986	pathogenic	-1.09	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/Q	0.9964	likely_pathogenic	0.9963	pathogenic	-1.201	Destabilizing	1.0	D	0.882	deleterious	D	0.650817787	None	None	N
P/R	0.9949	likely_pathogenic	0.9939	pathogenic	-0.82	Destabilizing	1.0	D	0.883	deleterious	D	0.650817787	None	None	N
P/S	0.9828	likely_pathogenic	0.9841	pathogenic	-1.718	Destabilizing	1.0	D	0.882	deleterious	D	0.634162653	None	None	N
P/T	0.981	likely_pathogenic	0.983	pathogenic	-1.544	Destabilizing	0.999	D	0.872	deleterious	D	0.650615983	None	None	N
P/V	0.9599	likely_pathogenic	0.9617	pathogenic	-1.016	Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9998	pathogenic	-1.483	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/Y	0.9993	likely_pathogenic	0.9993	pathogenic	-1.17	Destabilizing	1.0	D	0.893	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.