TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1755	5488;5489;5490	chr2:178776601;178776600;178776599	chr2:179641328;179641327;179641326
N2AB	1755	5488;5489;5490	chr2:178776601;178776600;178776599	chr2:179641328;179641327;179641326
N2A	1755	5488;5489;5490	chr2:178776601;178776600;178776599	chr2:179641328;179641327;179641326
N2B	1709	5350;5351;5352	chr2:178776601;178776600;178776599	chr2:179641328;179641327;179641326
Novex-1	1709	5350;5351;5352	chr2:178776601;178776600;178776599	chr2:179641328;179641327;179641326
Novex-2	1709	5350;5351;5352	chr2:178776601;178776600;178776599	chr2:179641328;179641327;179641326
Novex-3	1755	5488;5489;5490	chr2:178776601;178776600;178776599	chr2:179641328;179641327;179641326

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-8
• Domain position: 53
• Structural Position: 127
• Q(SASA): 0.4782
• 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
N/D	None	None	0.999	N	0.771	0.521	0.322786055943	gnomAD-4.0.0	1.59077E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02151E-05
N/H	rs559024675	-0.58	1.0	N	0.723	0.501	0.28297238246	gnomAD-2.1.1	3.99E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.83E-06	0
N/H	rs559024675	-0.58	1.0	N	0.723	0.501	0.28297238246	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/H	rs559024675	-0.58	1.0	N	0.723	0.501	0.28297238246	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	1E-03	None	None	None	0	None
N/H	rs559024675	-0.58	1.0	N	0.723	0.501	0.28297238246	gnomAD-4.0.0	6.56478E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.4699E-05	0	0
N/S	rs201904897	0.093	0.999	N	0.741	0.43	None	gnomAD-2.1.1	4.25E-05	None	None	None	None	I	None	4.01E-05	0	None	0	0	None	0	None	0	8.55E-05	0
N/S	rs201904897	0.093	0.999	N	0.741	0.43	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	7.35E-05	0	0
N/S	rs201904897	0.093	0.999	N	0.741	0.43	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	1E-03	None	None	None	0	None
N/S	rs201904897	0.093	0.999	N	0.741	0.43	None	gnomAD-4.0.0	5.32817E-05	None	None	None	None	I	None	2.66496E-05	0	None	0	0	None	0	0	6.94913E-05	0	3.19949E-05

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
N/A	0.7893	likely_pathogenic	0.7801	pathogenic	-0.405	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
N/C	0.7566	likely_pathogenic	0.7344	pathogenic	0.371	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
N/D	0.6173	likely_pathogenic	0.6505	pathogenic	-0.044	Destabilizing	0.999	D	0.771	deleterious	N	0.511401101	None	None	I
N/E	0.9069	likely_pathogenic	0.9093	pathogenic	-0.046	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
N/F	0.9479	likely_pathogenic	0.9422	pathogenic	-0.574	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
N/G	0.7127	likely_pathogenic	0.7292	pathogenic	-0.639	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	I
N/H	0.3625	ambiguous	0.3289	benign	-0.681	Destabilizing	1.0	D	0.723	prob.delet.	N	0.452454441	None	None	I
N/I	0.8807	likely_pathogenic	0.8822	pathogenic	0.138	Stabilizing	1.0	D	0.763	deleterious	D	0.58910777	None	None	I
N/K	0.9225	likely_pathogenic	0.9351	pathogenic	0.006	Stabilizing	1.0	D	0.763	deleterious	N	0.506630887	None	None	I
N/L	0.7807	likely_pathogenic	0.7801	pathogenic	0.138	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
N/M	0.8745	likely_pathogenic	0.8641	pathogenic	0.537	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
N/P	0.9344	likely_pathogenic	0.927	pathogenic	-0.014	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
N/Q	0.8101	likely_pathogenic	0.7922	pathogenic	-0.453	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
N/R	0.8844	likely_pathogenic	0.8957	pathogenic	None	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
N/S	0.1519	likely_benign	0.1481	benign	-0.26	Destabilizing	0.999	D	0.741	deleterious	N	0.489462684	None	None	I
N/T	0.474	ambiguous	0.484	ambiguous	-0.104	Destabilizing	0.999	D	0.76	deleterious	N	0.508561728	None	None	I
N/V	0.8419	likely_pathogenic	0.8359	pathogenic	-0.014	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
N/W	0.9695	likely_pathogenic	0.963	pathogenic	-0.488	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
N/Y	0.6523	likely_pathogenic	0.624	pathogenic	-0.246	Destabilizing	1.0	D	0.741	deleterious	N	0.510080743	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.