TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22528	67807;67808;67809	chr2:178579615;178579614;178579613	chr2:179444342;179444341;179444340
N2AB	20887	62884;62885;62886	chr2:178579615;178579614;178579613	chr2:179444342;179444341;179444340
N2A	19960	60103;60104;60105	chr2:178579615;178579614;178579613	chr2:179444342;179444341;179444340
N2B	13463	40612;40613;40614	chr2:178579615;178579614;178579613	chr2:179444342;179444341;179444340
Novex-1	13588	40987;40988;40989	chr2:178579615;178579614;178579613	chr2:179444342;179444341;179444340
Novex-2	13655	41188;41189;41190	chr2:178579615;178579614;178579613	chr2:179444342;179444341;179444340
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-51
• Domain position: 78
• Structural Position: 113
• Q(SASA): 0.7439
• 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/K	rs1416365418	0.77	0.645	N	0.513	0.299	0.264081493735	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs1416365418	0.77	0.645	N	0.513	0.299	0.264081493735	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1416365418	0.77	0.645	N	0.513	0.299	0.264081493735	gnomAD-4.0.0	3.84521E-06	None	None	None	None	I	None	1.69153E-05	0	None	0	0	None	0	0	4.789E-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	0.1742	likely_benign	0.1973	benign	-0.424	Destabilizing	0.645	D	0.543	neutral	N	0.451485806	None	None	I
E/C	0.8623	likely_pathogenic	0.8903	pathogenic	0.106	Stabilizing	0.995	D	0.695	prob.neutral	None	None	None	None	I
E/D	0.1296	likely_benign	0.144	benign	-0.354	Destabilizing	0.002	N	0.257	neutral	N	0.439519373	None	None	I
E/F	0.7947	likely_pathogenic	0.8562	pathogenic	-0.39	Destabilizing	0.995	D	0.604	neutral	None	None	None	None	I
E/G	0.2013	likely_benign	0.2238	benign	-0.626	Destabilizing	0.645	D	0.467	neutral	N	0.497946027	None	None	I
E/H	0.5464	ambiguous	0.6164	pathogenic	-0.326	Destabilizing	0.995	D	0.543	neutral	None	None	None	None	I
E/I	0.3324	likely_benign	0.4099	ambiguous	0.073	Stabilizing	0.945	D	0.617	neutral	None	None	None	None	I
E/K	0.1683	likely_benign	0.1988	benign	0.392	Stabilizing	0.645	D	0.513	neutral	N	0.435305632	None	None	I
E/L	0.4356	ambiguous	0.5119	ambiguous	0.073	Stabilizing	0.945	D	0.589	neutral	None	None	None	None	I
E/M	0.485	ambiguous	0.5793	pathogenic	0.307	Stabilizing	0.995	D	0.606	neutral	None	None	None	None	I
E/N	0.2994	likely_benign	0.3676	ambiguous	0.09	Stabilizing	0.809	D	0.525	neutral	None	None	None	None	I
E/P	0.6539	likely_pathogenic	0.6626	pathogenic	-0.073	Destabilizing	0.945	D	0.538	neutral	None	None	None	None	I
E/Q	0.1631	likely_benign	0.1905	benign	0.122	Stabilizing	0.864	D	0.488	neutral	N	0.477672329	None	None	I
E/R	0.2791	likely_benign	0.3238	benign	0.478	Stabilizing	0.945	D	0.556	neutral	None	None	None	None	I
E/S	0.2343	likely_benign	0.2697	benign	-0.067	Destabilizing	0.547	D	0.512	neutral	None	None	None	None	I
E/T	0.2679	likely_benign	0.3123	benign	0.1	Stabilizing	0.894	D	0.505	neutral	None	None	None	None	I
E/V	0.2292	likely_benign	0.2822	benign	-0.073	Destabilizing	0.928	D	0.549	neutral	N	0.480173917	None	None	I
E/W	0.9117	likely_pathogenic	0.9371	pathogenic	-0.253	Destabilizing	0.995	D	0.701	prob.neutral	None	None	None	None	I
E/Y	0.6776	likely_pathogenic	0.7531	pathogenic	-0.144	Destabilizing	0.995	D	0.583	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.