TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18025	54298;54299;54300	chr2:178605104;178605103;178605102	chr2:179469831;179469830;179469829
N2AB	16384	49375;49376;49377	chr2:178605104;178605103;178605102	chr2:179469831;179469830;179469829
N2A	15457	46594;46595;46596	chr2:178605104;178605103;178605102	chr2:179469831;179469830;179469829
N2B	8960	27103;27104;27105	chr2:178605104;178605103;178605102	chr2:179469831;179469830;179469829
Novex-1	9085	27478;27479;27480	chr2:178605104;178605103;178605102	chr2:179469831;179469830;179469829
Novex-2	9152	27679;27680;27681	chr2:178605104;178605103;178605102	chr2:179469831;179469830;179469829
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: Ig-114
• Domain position: 58
• Structural Position: 131
• Q(SASA): 0.3994
• 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
E/G	None	None	0.625	N	0.612	0.112	0.214338557667	gnomAD-4.0.0	1.59332E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86226E-06	0	0
E/K	rs2054470493	None	0.801	N	0.563	0.138	0.191931220699	gnomAD-4.0.0	1.5934E-06	None	None	None	None	N	None	0	0	None	0	2.78164E-05	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	0.2205	likely_benign	0.2148	benign	-0.341	Destabilizing	0.625	D	0.575	neutral	N	0.438276074	None	None	N
E/C	0.8851	likely_pathogenic	0.8959	pathogenic	0.161	Stabilizing	0.998	D	0.609	neutral	None	None	None	None	N
E/D	0.1975	likely_benign	0.1811	benign	-0.751	Destabilizing	0.012	N	0.238	neutral	N	0.408262598	None	None	N
E/F	0.7644	likely_pathogenic	0.7628	pathogenic	-0.613	Destabilizing	0.974	D	0.627	neutral	None	None	None	None	N
E/G	0.3802	ambiguous	0.3497	ambiguous	-0.579	Destabilizing	0.625	D	0.612	neutral	N	0.411321546	None	None	N
E/H	0.5607	ambiguous	0.5676	pathogenic	-0.897	Destabilizing	0.974	D	0.611	neutral	None	None	None	None	N
E/I	0.3335	likely_benign	0.356	ambiguous	0.26	Stabilizing	0.728	D	0.623	neutral	None	None	None	None	N
E/K	0.2921	likely_benign	0.2949	benign	0.184	Stabilizing	0.801	D	0.563	neutral	N	0.445356762	None	None	N
E/L	0.476	ambiguous	0.4881	ambiguous	0.26	Stabilizing	0.728	D	0.605	neutral	None	None	None	None	N
E/M	0.4936	ambiguous	0.5046	ambiguous	0.678	Stabilizing	0.974	D	0.622	neutral	None	None	None	None	N
E/N	0.3637	ambiguous	0.3549	ambiguous	-0.04	Destabilizing	0.029	N	0.26	neutral	None	None	None	None	N
E/P	0.9829	likely_pathogenic	0.9725	pathogenic	0.081	Stabilizing	0.974	D	0.643	neutral	None	None	None	None	N
E/Q	0.2115	likely_benign	0.2089	benign	-0.022	Destabilizing	0.891	D	0.559	neutral	N	0.42900323	None	None	N
E/R	0.4536	ambiguous	0.4536	ambiguous	0.101	Stabilizing	0.915	D	0.59	neutral	None	None	None	None	N
E/S	0.2879	likely_benign	0.273	benign	-0.238	Destabilizing	0.525	D	0.569	neutral	None	None	None	None	N
E/T	0.2374	likely_benign	0.2465	benign	-0.045	Destabilizing	0.067	N	0.361	neutral	None	None	None	None	N
E/V	0.2125	likely_benign	0.2232	benign	0.081	Stabilizing	0.051	N	0.511	neutral	N	0.45382153	None	None	N
E/W	0.9332	likely_pathogenic	0.9327	pathogenic	-0.62	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
E/Y	0.7141	likely_pathogenic	0.7067	pathogenic	-0.39	Destabilizing	0.991	D	0.637	neutral	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.