TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28104	84535;84536;84537	chr2:178561822;178561821;178561820	chr2:179426549;179426548;179426547
N2AB	26463	79612;79613;79614	chr2:178561822;178561821;178561820	chr2:179426549;179426548;179426547
N2A	25536	76831;76832;76833	chr2:178561822;178561821;178561820	chr2:179426549;179426548;179426547
N2B	19039	57340;57341;57342	chr2:178561822;178561821;178561820	chr2:179426549;179426548;179426547
Novex-1	19164	57715;57716;57717	chr2:178561822;178561821;178561820	chr2:179426549;179426548;179426547
Novex-2	19231	57916;57917;57918	chr2:178561822;178561821;178561820	chr2:179426549;179426548;179426547
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-92
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.2772
• 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
I/V	rs778359308	-1.038	None	N	0.133	0.131	0.223847106136	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs778359308	-1.038	None	N	0.133	0.131	0.223847106136	gnomAD-4.0.0	3.18337E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88296E-05	0	0	1.43291E-05	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
I/A	0.128	likely_benign	0.1321	benign	-1.333	Destabilizing	0.016	N	0.447	neutral	None	None	None	None	I
I/C	0.4404	ambiguous	0.4448	ambiguous	-0.773	Destabilizing	0.676	D	0.551	neutral	None	None	None	None	I
I/D	0.4487	ambiguous	0.4347	ambiguous	-0.815	Destabilizing	0.214	N	0.591	neutral	None	None	None	None	I
I/E	0.3489	ambiguous	0.3428	ambiguous	-0.86	Destabilizing	0.072	N	0.564	neutral	None	None	None	None	I
I/F	0.1433	likely_benign	0.1426	benign	-0.991	Destabilizing	0.214	N	0.463	neutral	None	None	None	None	I
I/G	0.3607	ambiguous	0.3561	ambiguous	-1.595	Destabilizing	0.072	N	0.561	neutral	None	None	None	None	I
I/H	0.3315	likely_benign	0.3266	benign	-0.773	Destabilizing	0.864	D	0.579	neutral	None	None	None	None	I
I/K	0.2615	likely_benign	0.2458	benign	-0.937	Destabilizing	0.029	N	0.526	neutral	N	0.447464065	None	None	I
I/L	0.0836	likely_benign	0.0891	benign	-0.716	Destabilizing	None	N	0.131	neutral	N	0.468706129	None	None	I
I/M	0.0737	likely_benign	0.0763	benign	-0.535	Destabilizing	0.171	N	0.497	neutral	N	0.45443011	None	None	I
I/N	0.1475	likely_benign	0.1496	benign	-0.688	Destabilizing	0.214	N	0.586	neutral	None	None	None	None	I
I/P	0.2518	likely_benign	0.2377	benign	-0.889	Destabilizing	0.356	N	0.591	neutral	None	None	None	None	I
I/Q	0.2593	likely_benign	0.2579	benign	-0.92	Destabilizing	0.214	N	0.586	neutral	None	None	None	None	I
I/R	0.1878	likely_benign	0.1841	benign	-0.275	Destabilizing	None	N	0.42	neutral	N	0.464356315	None	None	I
I/S	0.1305	likely_benign	0.1354	benign	-1.222	Destabilizing	0.038	N	0.519	neutral	None	None	None	None	I
I/T	0.0736	likely_benign	0.08	benign	-1.16	Destabilizing	None	N	0.282	neutral	N	0.369926002	None	None	I
I/V	0.058	likely_benign	0.0591	benign	-0.889	Destabilizing	None	N	0.133	neutral	N	0.429513023	None	None	I
I/W	0.6756	likely_pathogenic	0.6574	pathogenic	-1.016	Destabilizing	0.864	D	0.616	neutral	None	None	None	None	I
I/Y	0.3977	ambiguous	0.3811	ambiguous	-0.815	Destabilizing	0.356	N	0.568	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.