TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5214	15865;15866;15867	chr2:178733749;178733748;178733747	chr2:179598476;179598475;179598474
N2AB	4897	14914;14915;14916	chr2:178733749;178733748;178733747	chr2:179598476;179598475;179598474
N2A	3970	12133;12134;12135	chr2:178733749;178733748;178733747	chr2:179598476;179598475;179598474
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-35
• Domain position: 47
• Structural Position: 121
• 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
I/V	None	None	0.001	N	0.195	0.078	0.386721274199	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88232E-05	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
I/A	0.3275	likely_benign	0.4153	ambiguous	-2.457	Highly Destabilizing	0.218	N	0.658	neutral	None	None	None	None	N
I/C	0.4854	ambiguous	0.6009	pathogenic	-1.606	Destabilizing	0.973	D	0.727	prob.delet.	None	None	None	None	N
I/D	0.6327	likely_pathogenic	0.7438	pathogenic	-2.649	Highly Destabilizing	0.967	D	0.809	deleterious	None	None	None	None	N
I/E	0.444	ambiguous	0.5636	ambiguous	-2.524	Highly Destabilizing	0.906	D	0.798	deleterious	None	None	None	None	N
I/F	0.0989	likely_benign	0.1177	benign	-1.555	Destabilizing	0.782	D	0.653	neutral	N	0.50931571	None	None	N
I/G	0.5175	ambiguous	0.6345	pathogenic	-2.915	Highly Destabilizing	0.906	D	0.775	deleterious	None	None	None	None	N
I/H	0.3452	ambiguous	0.4768	ambiguous	-2.328	Highly Destabilizing	0.991	D	0.79	deleterious	None	None	None	None	N
I/K	0.3269	likely_benign	0.4469	ambiguous	-2.103	Highly Destabilizing	0.906	D	0.793	deleterious	None	None	None	None	N
I/L	0.1012	likely_benign	0.1156	benign	-1.178	Destabilizing	0.001	N	0.214	neutral	N	0.502227031	None	None	N
I/M	0.0775	likely_benign	0.0904	benign	-0.902	Destabilizing	0.782	D	0.663	neutral	D	0.620840228	None	None	N
I/N	0.1822	likely_benign	0.2621	benign	-2.119	Highly Destabilizing	0.957	D	0.811	deleterious	D	0.690610545	None	None	N
I/P	0.7903	likely_pathogenic	0.8265	pathogenic	-1.581	Destabilizing	0.967	D	0.81	deleterious	None	None	None	None	N
I/Q	0.3301	likely_benign	0.4434	ambiguous	-2.145	Highly Destabilizing	0.967	D	0.801	deleterious	None	None	None	None	N
I/R	0.2163	likely_benign	0.3003	benign	-1.564	Destabilizing	0.906	D	0.809	deleterious	None	None	None	None	N
I/S	0.2474	likely_benign	0.3387	benign	-2.728	Highly Destabilizing	0.782	D	0.734	prob.delet.	D	0.62096376	None	None	N
I/T	0.1997	likely_benign	0.255	benign	-2.482	Highly Destabilizing	0.505	D	0.682	prob.neutral	D	0.576158116	None	None	N
I/V	0.0722	likely_benign	0.0786	benign	-1.581	Destabilizing	0.001	N	0.195	neutral	N	0.499259993	None	None	N
I/W	0.5176	ambiguous	0.5963	pathogenic	-1.878	Destabilizing	0.991	D	0.769	deleterious	None	None	None	None	N
I/Y	0.236	likely_benign	0.3021	benign	-1.653	Destabilizing	0.906	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.