TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23981	72166;72167;72168	chr2:178574191;178574190;178574189	chr2:179438918;179438917;179438916
N2AB	22340	67243;67244;67245	chr2:178574191;178574190;178574189	chr2:179438918;179438917;179438916
N2A	21413	64462;64463;64464	chr2:178574191;178574190;178574189	chr2:179438918;179438917;179438916
N2B	14916	44971;44972;44973	chr2:178574191;178574190;178574189	chr2:179438918;179438917;179438916
Novex-1	15041	45346;45347;45348	chr2:178574191;178574190;178574189	chr2:179438918;179438917;179438916
Novex-2	15108	45547;45548;45549	chr2:178574191;178574190;178574189	chr2:179438918;179438917;179438916
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-62
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.5756
• 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
E/D	rs1559434457	None	0.999	N	0.445	0.191	0.222439326576	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/D	rs1559434457	None	0.999	N	0.445	0.191	0.222439326576	gnomAD-4.0.0	1.59188E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85923E-06	0	0
E/Q	rs794729246	None	1.0	N	0.598	0.24	0.290590437066	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/Q	rs794729246	None	1.0	N	0.598	0.24	0.290590437066	gnomAD-4.0.0	6.57436E-06	None	None	None	None	I	None	0	6.55394E-05	None	0	0	None	0	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
E/A	0.2655	likely_benign	0.2859	benign	-0.341	Destabilizing	0.999	D	0.648	neutral	N	0.50626444	None	None	I
E/C	0.9055	likely_pathogenic	0.914	pathogenic	-0.404	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
E/D	0.1232	likely_benign	0.1236	benign	-0.476	Destabilizing	0.999	D	0.445	neutral	N	0.429249238	None	None	I
E/F	0.9032	likely_pathogenic	0.9197	pathogenic	0.073	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	I
E/G	0.1843	likely_benign	0.2097	benign	-0.587	Destabilizing	1.0	D	0.613	neutral	N	0.509056816	None	None	I
E/H	0.6344	likely_pathogenic	0.6638	pathogenic	0.43	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	I
E/I	0.6482	likely_pathogenic	0.6812	pathogenic	0.29	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
E/K	0.2873	likely_benign	0.3154	benign	0.041	Stabilizing	0.999	D	0.585	neutral	N	0.511902333	None	None	I
E/L	0.6394	likely_pathogenic	0.6858	pathogenic	0.29	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	I
E/M	0.6928	likely_pathogenic	0.7329	pathogenic	0.158	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	I
E/N	0.3167	likely_benign	0.3355	benign	-0.428	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
E/P	0.849	likely_pathogenic	0.871	pathogenic	0.1	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
E/Q	0.2039	likely_benign	0.2183	benign	-0.334	Destabilizing	1.0	D	0.598	neutral	N	0.505515078	None	None	I
E/R	0.4384	ambiguous	0.4679	ambiguous	0.452	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	I
E/S	0.2922	likely_benign	0.3177	benign	-0.611	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
E/T	0.3449	ambiguous	0.3661	ambiguous	-0.401	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
E/V	0.4218	ambiguous	0.4477	ambiguous	0.1	Stabilizing	1.0	D	0.65	neutral	N	0.518060301	None	None	I
E/W	0.9502	likely_pathogenic	0.9583	pathogenic	0.273	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
E/Y	0.7984	likely_pathogenic	0.8256	pathogenic	0.322	Stabilizing	1.0	D	0.644	neutral	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.