TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32288	97087;97088;97089	chr2:178543111;178543110;178543109	chr2:179407838;179407837;179407836
N2AB	30647	92164;92165;92166	chr2:178543111;178543110;178543109	chr2:179407838;179407837;179407836
N2A	29720	89383;89384;89385	chr2:178543111;178543110;178543109	chr2:179407838;179407837;179407836
N2B	23223	69892;69893;69894	chr2:178543111;178543110;178543109	chr2:179407838;179407837;179407836
Novex-1	23348	70267;70268;70269	chr2:178543111;178543110;178543109	chr2:179407838;179407837;179407836
Novex-2	23415	70468;70469;70470	chr2:178543111;178543110;178543109	chr2:179407838;179407837;179407836
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: Fn3-123
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2294
• 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/A	None	None	0.002	N	0.482	0.234	0.0846915920261	gnomAD-4.0.0	4.11837E-06	None	None	None	None	I	None	0	0	None	0	7.57805E-05	None	0	0	2.70704E-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
P/A	0.1049	likely_benign	0.0935	benign	-1.742	Destabilizing	0.002	N	0.482	neutral	N	0.477063096	None	None	I
P/C	0.7332	likely_pathogenic	0.6796	pathogenic	-1.061	Destabilizing	0.962	D	0.873	deleterious	None	None	None	None	I
P/D	0.8612	likely_pathogenic	0.8293	pathogenic	-1.937	Destabilizing	0.452	N	0.779	deleterious	None	None	None	None	I
P/E	0.7528	likely_pathogenic	0.7065	pathogenic	-1.932	Destabilizing	0.567	D	0.759	deleterious	None	None	None	None	I
P/F	0.7591	likely_pathogenic	0.6784	pathogenic	-1.335	Destabilizing	0.997	D	0.879	deleterious	None	None	None	None	I
P/G	0.4285	ambiguous	0.4067	ambiguous	-2.05	Highly Destabilizing	0.546	D	0.717	prob.delet.	None	None	None	None	I
P/H	0.6922	likely_pathogenic	0.6149	pathogenic	-1.529	Destabilizing	0.997	D	0.843	deleterious	None	None	None	None	I
P/I	0.6485	likely_pathogenic	0.6036	pathogenic	-0.979	Destabilizing	0.977	D	0.854	deleterious	None	None	None	None	I
P/K	0.858	likely_pathogenic	0.83	pathogenic	-1.492	Destabilizing	0.977	D	0.775	deleterious	None	None	None	None	I
P/L	0.4188	ambiguous	0.3577	ambiguous	-0.979	Destabilizing	0.94	D	0.781	deleterious	N	0.510789617	None	None	I
P/M	0.654	likely_pathogenic	0.5893	pathogenic	-0.695	Destabilizing	0.992	D	0.845	deleterious	None	None	None	None	I
P/N	0.7868	likely_pathogenic	0.7353	pathogenic	-1.318	Destabilizing	0.913	D	0.837	deleterious	None	None	None	None	I
P/Q	0.6445	likely_pathogenic	0.5736	pathogenic	-1.528	Destabilizing	0.96	D	0.813	deleterious	D	0.524173839	None	None	I
P/R	0.7917	likely_pathogenic	0.7566	pathogenic	-0.854	Destabilizing	0.969	D	0.837	deleterious	N	0.512310555	None	None	I
P/S	0.2906	likely_benign	0.2458	benign	-1.775	Destabilizing	0.815	D	0.701	prob.neutral	N	0.495180578	None	None	I
P/T	0.3376	likely_benign	0.2866	benign	-1.681	Destabilizing	0.662	D	0.705	prob.neutral	N	0.5171724	None	None	I
P/V	0.4483	ambiguous	0.4192	ambiguous	-1.201	Destabilizing	0.786	D	0.723	prob.delet.	None	None	None	None	I
P/W	0.8651	likely_pathogenic	0.8191	pathogenic	-1.544	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	I
P/Y	0.7707	likely_pathogenic	0.7022	pathogenic	-1.289	Destabilizing	0.997	D	0.88	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.