TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21988	66187;66188;66189	chr2:178582494;178582493;178582492	chr2:179447221;179447220;179447219
N2AB	20347	61264;61265;61266	chr2:178582494;178582493;178582492	chr2:179447221;179447220;179447219
N2A	19420	58483;58484;58485	chr2:178582494;178582493;178582492	chr2:179447221;179447220;179447219
N2B	12923	38992;38993;38994	chr2:178582494;178582493;178582492	chr2:179447221;179447220;179447219
Novex-1	13048	39367;39368;39369	chr2:178582494;178582493;178582492	chr2:179447221;179447220;179447219
Novex-2	13115	39568;39569;39570	chr2:178582494;178582493;178582492	chr2:179447221;179447220;179447219
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: Fn3-47
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2097
• 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
I/L	None	None	0.993	N	0.405	0.394	0.670927618927	gnomAD-4.0.0	1.5932E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86157E-06	0	0
I/T	rs776884578	-1.866	1.0	D	0.825	0.591	0.787357044059	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
I/T	rs776884578	-1.866	1.0	D	0.825	0.591	0.787357044059	gnomAD-4.0.0	7.53029E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.27607E-04	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	0.9906	likely_pathogenic	0.9861	pathogenic	-2.359	Highly Destabilizing	0.999	D	0.674	neutral	None	None	None	None	I
I/C	0.991	likely_pathogenic	0.9876	pathogenic	-1.485	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
I/D	0.9992	likely_pathogenic	0.9991	pathogenic	-2.354	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
I/E	0.9969	likely_pathogenic	0.9966	pathogenic	-2.296	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
I/F	0.9778	likely_pathogenic	0.9676	pathogenic	-1.723	Destabilizing	1.0	D	0.839	deleterious	D	0.539349395	None	None	I
I/G	0.9983	likely_pathogenic	0.9977	pathogenic	-2.761	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
I/H	0.9989	likely_pathogenic	0.9984	pathogenic	-2.02	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
I/K	0.9937	likely_pathogenic	0.9915	pathogenic	-1.713	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
I/L	0.6552	likely_pathogenic	0.5298	ambiguous	-1.267	Destabilizing	0.993	D	0.405	neutral	N	0.491771353	None	None	I
I/M	0.7609	likely_pathogenic	0.6875	pathogenic	-0.885	Destabilizing	1.0	D	0.827	deleterious	D	0.54188429	None	None	I
I/N	0.9832	likely_pathogenic	0.9791	pathogenic	-1.639	Destabilizing	1.0	D	0.861	deleterious	D	0.536150299	None	None	I
I/P	0.984	likely_pathogenic	0.9774	pathogenic	-1.605	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
I/Q	0.9972	likely_pathogenic	0.9962	pathogenic	-1.79	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
I/R	0.9939	likely_pathogenic	0.9914	pathogenic	-1.076	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
I/S	0.9935	likely_pathogenic	0.991	pathogenic	-2.264	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.54213778	None	None	I
I/T	0.9771	likely_pathogenic	0.9694	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.825	deleterious	D	0.530781474	None	None	I
I/V	0.1625	likely_benign	0.1483	benign	-1.605	Destabilizing	0.993	D	0.391	neutral	N	0.491279132	None	None	I
I/W	0.9994	likely_pathogenic	0.9992	pathogenic	-1.91	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
I/Y	0.9961	likely_pathogenic	0.9942	pathogenic	-1.704	Destabilizing	1.0	D	0.858	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.