TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24986	75181;75182;75183	chr2:178571176;178571175;178571174	chr2:179435903;179435902;179435901
N2AB	23345	70258;70259;70260	chr2:178571176;178571175;178571174	chr2:179435903;179435902;179435901
N2A	22418	67477;67478;67479	chr2:178571176;178571175;178571174	chr2:179435903;179435902;179435901
N2B	15921	47986;47987;47988	chr2:178571176;178571175;178571174	chr2:179435903;179435902;179435901
Novex-1	16046	48361;48362;48363	chr2:178571176;178571175;178571174	chr2:179435903;179435902;179435901
Novex-2	16113	48562;48563;48564	chr2:178571176;178571175;178571174	chr2:179435903;179435902;179435901
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: Fn3-69
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2296
• 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	None	None	0.822	N	0.407	0.172	0.168933306366	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.4788	ambiguous	0.4745	ambiguous	-1.278	Destabilizing	0.698	D	0.523	neutral	N	0.470822126	None	None	I
E/C	0.9313	likely_pathogenic	0.926	pathogenic	-0.975	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	I
E/D	0.8386	likely_pathogenic	0.8478	pathogenic	-1.642	Destabilizing	0.822	D	0.407	neutral	N	0.503627275	None	None	I
E/F	0.9546	likely_pathogenic	0.9576	pathogenic	-1.263	Destabilizing	0.998	D	0.812	deleterious	None	None	None	None	I
E/G	0.7265	likely_pathogenic	0.7263	pathogenic	-1.646	Destabilizing	0.942	D	0.724	prob.delet.	N	0.503627275	None	None	I
E/H	0.8977	likely_pathogenic	0.8977	pathogenic	-1.486	Destabilizing	0.994	D	0.657	neutral	None	None	None	None	I
E/I	0.5293	ambiguous	0.5336	ambiguous	-0.256	Destabilizing	0.978	D	0.834	deleterious	None	None	None	None	I
E/K	0.459	ambiguous	0.4548	ambiguous	-1.509	Destabilizing	0.698	D	0.426	neutral	N	0.474634014	None	None	I
E/L	0.7365	likely_pathogenic	0.7537	pathogenic	-0.256	Destabilizing	0.956	D	0.737	prob.delet.	None	None	None	None	I
E/M	0.6199	likely_pathogenic	0.6293	pathogenic	0.359	Stabilizing	0.994	D	0.791	deleterious	None	None	None	None	I
E/N	0.8581	likely_pathogenic	0.8648	pathogenic	-1.713	Destabilizing	0.956	D	0.609	neutral	None	None	None	None	I
E/P	0.9985	likely_pathogenic	0.9983	pathogenic	-0.578	Destabilizing	0.978	D	0.789	deleterious	None	None	None	None	I
E/Q	0.2073	likely_benign	0.1945	benign	-1.492	Destabilizing	0.058	N	0.287	neutral	N	0.466796428	None	None	I
E/R	0.6536	likely_pathogenic	0.6362	pathogenic	-1.392	Destabilizing	0.915	D	0.597	neutral	None	None	None	None	I
E/S	0.6277	likely_pathogenic	0.6323	pathogenic	-2.264	Highly Destabilizing	0.754	D	0.434	neutral	None	None	None	None	I
E/T	0.6226	likely_pathogenic	0.6276	pathogenic	-1.935	Destabilizing	0.956	D	0.713	prob.delet.	None	None	None	None	I
E/V	0.3528	ambiguous	0.3565	ambiguous	-0.578	Destabilizing	0.942	D	0.747	deleterious	N	0.472007433	None	None	I
E/W	0.9885	likely_pathogenic	0.9875	pathogenic	-1.37	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	I
E/Y	0.9465	likely_pathogenic	0.9446	pathogenic	-1.111	Destabilizing	0.978	D	0.821	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.