TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30700	92323;92324;92325	chr2:178549624;178549623;178549622	chr2:179414351;179414350;179414349
N2AB	29059	87400;87401;87402	chr2:178549624;178549623;178549622	chr2:179414351;179414350;179414349
N2A	28132	84619;84620;84621	chr2:178549624;178549623;178549622	chr2:179414351;179414350;179414349
N2B	21635	65128;65129;65130	chr2:178549624;178549623;178549622	chr2:179414351;179414350;179414349
Novex-1	21760	65503;65504;65505	chr2:178549624;178549623;178549622	chr2:179414351;179414350;179414349
Novex-2	21827	65704;65705;65706	chr2:178549624;178549623;178549622	chr2:179414351;179414350;179414349
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-111
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.5837
• 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
F/S	rs746552047	-0.633	0.879	N	0.626	0.38	0.590258251349	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
F/S	rs746552047	-0.633	0.879	N	0.626	0.38	0.590258251349	gnomAD-4.0.0	6.36551E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.14345E-05	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
F/A	0.7188	likely_pathogenic	0.8086	pathogenic	-0.97	Destabilizing	0.575	D	0.615	neutral	None	None	None	None	I
F/C	0.4809	ambiguous	0.5997	pathogenic	-0.337	Destabilizing	0.988	D	0.703	prob.neutral	N	0.477056254	None	None	I
F/D	0.9102	likely_pathogenic	0.9402	pathogenic	0.668	Stabilizing	0.906	D	0.697	prob.neutral	None	None	None	None	I
F/E	0.9334	likely_pathogenic	0.9567	pathogenic	0.641	Stabilizing	0.906	D	0.697	prob.neutral	None	None	None	None	I
F/G	0.9219	likely_pathogenic	0.942	pathogenic	-1.161	Destabilizing	0.906	D	0.656	neutral	None	None	None	None	I
F/H	0.5926	likely_pathogenic	0.6545	pathogenic	0.232	Stabilizing	0.991	D	0.594	neutral	None	None	None	None	I
F/I	0.2962	likely_benign	0.4579	ambiguous	-0.488	Destabilizing	0.003	N	0.389	neutral	N	0.447021348	None	None	I
F/K	0.9471	likely_pathogenic	0.9621	pathogenic	-0.098	Destabilizing	0.906	D	0.701	prob.neutral	None	None	None	None	I
F/L	0.8931	likely_pathogenic	0.9375	pathogenic	-0.488	Destabilizing	0.003	N	0.242	neutral	N	0.478960408	None	None	I
F/M	0.5862	likely_pathogenic	0.6869	pathogenic	-0.387	Destabilizing	0.826	D	0.481	neutral	None	None	None	None	I
F/N	0.6912	likely_pathogenic	0.7888	pathogenic	-0.053	Destabilizing	0.967	D	0.703	prob.neutral	None	None	None	None	I
F/P	0.9949	likely_pathogenic	0.9965	pathogenic	-0.629	Destabilizing	0.967	D	0.701	prob.neutral	None	None	None	None	I
F/Q	0.8744	likely_pathogenic	0.9129	pathogenic	-0.128	Destabilizing	0.967	D	0.702	prob.neutral	None	None	None	None	I
F/R	0.8985	likely_pathogenic	0.9251	pathogenic	0.392	Stabilizing	0.906	D	0.704	prob.neutral	None	None	None	None	I
F/S	0.6101	likely_pathogenic	0.7172	pathogenic	-0.728	Destabilizing	0.879	D	0.626	neutral	N	0.467396621	None	None	I
F/T	0.7085	likely_pathogenic	0.8083	pathogenic	-0.661	Destabilizing	0.826	D	0.613	neutral	None	None	None	None	I
F/V	0.3323	likely_benign	0.4933	ambiguous	-0.629	Destabilizing	0.068	N	0.563	neutral	N	0.445173122	None	None	I
F/W	0.4595	ambiguous	0.4709	ambiguous	-0.324	Destabilizing	0.991	D	0.51	neutral	None	None	None	None	I
F/Y	0.1161	likely_benign	0.1421	benign	-0.296	Destabilizing	0.674	D	0.484	neutral	N	0.360077154	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.