TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7023	21292;21293;21294	chr2:178724308;178724307;178724306	chr2:179589035;179589034;179589033
N2AB	6706	20341;20342;20343	chr2:178724308;178724307;178724306	chr2:179589035;179589034;179589033
N2A	5779	17560;17561;17562	chr2:178724308;178724307;178724306	chr2:179589035;179589034;179589033
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-54
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.4099
• 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
Q/P	rs753621469	0.062	0.784	N	0.479	0.389	0.440077040801	gnomAD-2.1.1	7.14E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.56E-05	0
Q/P	rs753621469	0.062	0.784	N	0.479	0.389	0.440077040801	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Q/P	rs753621469	0.062	0.784	N	0.479	0.389	0.440077040801	gnomAD-4.0.0	5.57834E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.62959E-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
Q/A	0.2473	likely_benign	0.2805	benign	-0.346	Destabilizing	0.176	N	0.371	neutral	None	None	None	None	I
Q/C	0.5558	ambiguous	0.5955	pathogenic	-0.121	Destabilizing	0.995	D	0.481	neutral	None	None	None	None	I
Q/D	0.4858	ambiguous	0.5275	ambiguous	-1.319	Destabilizing	0.003	N	0.095	neutral	None	None	None	None	I
Q/E	0.0977	likely_benign	0.0995	benign	-1.239	Destabilizing	0.139	N	0.225	neutral	N	0.410517122	None	None	I
Q/F	0.6327	likely_pathogenic	0.6851	pathogenic	-0.363	Destabilizing	0.981	D	0.501	neutral	None	None	None	None	I
Q/G	0.2913	likely_benign	0.3306	benign	-0.659	Destabilizing	0.495	N	0.498	neutral	None	None	None	None	I
Q/H	0.1945	likely_benign	0.2146	benign	-0.804	Destabilizing	0.975	D	0.434	neutral	N	0.462332809	None	None	I
Q/I	0.387	ambiguous	0.4137	ambiguous	0.431	Stabilizing	0.944	D	0.517	neutral	None	None	None	None	I
Q/K	0.0889	likely_benign	0.0867	benign	-0.187	Destabilizing	0.002	N	0.117	neutral	N	0.40199364	None	None	I
Q/L	0.1612	likely_benign	0.1722	benign	0.431	Stabilizing	0.642	D	0.457	neutral	N	0.488593904	None	None	I
Q/M	0.3549	ambiguous	0.3734	ambiguous	0.868	Stabilizing	0.981	D	0.448	neutral	None	None	None	None	I
Q/N	0.3406	ambiguous	0.3706	ambiguous	-0.807	Destabilizing	0.495	N	0.255	neutral	None	None	None	None	I
Q/P	0.812	likely_pathogenic	0.8303	pathogenic	0.203	Stabilizing	0.784	D	0.479	neutral	N	0.514761785	None	None	I
Q/R	0.0899	likely_benign	0.0974	benign	-0.123	Destabilizing	0.473	N	0.261	neutral	N	0.425102573	None	None	I
Q/S	0.2605	likely_benign	0.3087	benign	-0.797	Destabilizing	0.037	N	0.093	neutral	None	None	None	None	I
Q/T	0.1883	likely_benign	0.2119	benign	-0.543	Destabilizing	0.329	N	0.396	neutral	None	None	None	None	I
Q/V	0.269	likely_benign	0.2878	benign	0.203	Stabilizing	0.828	D	0.489	neutral	None	None	None	None	I
Q/W	0.4384	ambiguous	0.4731	ambiguous	-0.352	Destabilizing	0.995	D	0.507	neutral	None	None	None	None	I
Q/Y	0.4402	ambiguous	0.4821	ambiguous	0.005	Stabilizing	0.981	D	0.457	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.