TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30159	90700;90701;90702	chr2:178552425;178552424;178552423	chr2:179417152;179417151;179417150
N2AB	28518	85777;85778;85779	chr2:178552425;178552424;178552423	chr2:179417152;179417151;179417150
N2A	27591	82996;82997;82998	chr2:178552425;178552424;178552423	chr2:179417152;179417151;179417150
N2B	21094	63505;63506;63507	chr2:178552425;178552424;178552423	chr2:179417152;179417151;179417150
Novex-1	21219	63880;63881;63882	chr2:178552425;178552424;178552423	chr2:179417152;179417151;179417150
Novex-2	21286	64081;64082;64083	chr2:178552425;178552424;178552423	chr2:179417152;179417151;179417150
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-148
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.6002
• Predicted PPI site: I

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/H	rs1699807023	None	1.0	D	0.719	0.656	0.746219950608	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/H	rs1699807023	None	1.0	D	0.719	0.656	0.746219950608	gnomAD-4.0.0	6.57436E-06	None	None	None	None	I	None	2.41499E-05	0	None	0	0	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
P/A	0.9541	likely_pathogenic	0.9548	pathogenic	-0.588	Destabilizing	1.0	D	0.733	prob.delet.	D	0.547630823	None	None	I
P/C	0.9946	likely_pathogenic	0.9949	pathogenic	-0.564	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
P/D	0.9923	likely_pathogenic	0.9927	pathogenic	-0.523	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
P/E	0.9868	likely_pathogenic	0.9878	pathogenic	-0.638	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
P/F	0.9975	likely_pathogenic	0.9973	pathogenic	-0.794	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
P/G	0.9823	likely_pathogenic	0.9805	pathogenic	-0.728	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
P/H	0.9856	likely_pathogenic	0.9869	pathogenic	-0.327	Destabilizing	1.0	D	0.719	prob.delet.	D	0.626869134	None	None	I
P/I	0.9795	likely_pathogenic	0.9772	pathogenic	-0.366	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
P/K	0.9866	likely_pathogenic	0.9872	pathogenic	-0.601	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
P/L	0.9457	likely_pathogenic	0.9507	pathogenic	-0.366	Destabilizing	1.0	D	0.715	prob.delet.	D	0.626869134	None	None	I
P/M	0.9814	likely_pathogenic	0.9825	pathogenic	-0.367	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
P/N	0.9891	likely_pathogenic	0.9874	pathogenic	-0.278	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
P/Q	0.9786	likely_pathogenic	0.9796	pathogenic	-0.54	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
P/R	0.9748	likely_pathogenic	0.977	pathogenic	-0.041	Destabilizing	1.0	D	0.728	prob.delet.	D	0.626465525	None	None	I
P/S	0.9859	likely_pathogenic	0.9866	pathogenic	-0.603	Destabilizing	1.0	D	0.729	prob.delet.	D	0.547123844	None	None	I
P/T	0.9563	likely_pathogenic	0.9595	pathogenic	-0.623	Destabilizing	1.0	D	0.722	prob.delet.	D	0.626465525	None	None	I
P/V	0.9575	likely_pathogenic	0.955	pathogenic	-0.406	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
P/W	0.9978	likely_pathogenic	0.998	pathogenic	-0.883	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
P/Y	0.9946	likely_pathogenic	0.994	pathogenic	-0.599	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I

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.