TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24256	72991;72992;72993	chr2:178573366;178573365;178573364	chr2:179438093;179438092;179438091
N2AB	22615	68068;68069;68070	chr2:178573366;178573365;178573364	chr2:179438093;179438092;179438091
N2A	21688	65287;65288;65289	chr2:178573366;178573365;178573364	chr2:179438093;179438092;179438091
N2B	15191	45796;45797;45798	chr2:178573366;178573365;178573364	chr2:179438093;179438092;179438091
Novex-1	15316	46171;46172;46173	chr2:178573366;178573365;178573364	chr2:179438093;179438092;179438091
Novex-2	15383	46372;46373;46374	chr2:178573366;178573365;178573364	chr2:179438093;179438092;179438091
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-64
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1045
• 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
N/D	rs187868672	-1.704	0.684	N	0.547	0.203	None	gnomAD-2.1.1	4.67105E-04	None	None	None	None	N	None	4.28E-05	4.36E-05	None	0	0	None	0	None	9.54E-05	9.04001E-04	3.85356E-04
N/D	rs187868672	-1.704	0.684	N	0.547	0.203	None	gnomAD-3.1.2	2.03859E-04	None	None	None	None	N	None	7.24E-05	6.56E-05	0	0	0	None	1.88501E-04	0	3.52931E-04	2.07125E-04	0
N/D	rs187868672	-1.704	0.684	N	0.547	0.203	None	gnomAD-4.0.0	2.786E-04	None	None	None	None	N	None	6.94502E-05	4.30571E-05	None	0	0	None	1.64198E-04	8.84017E-04	3.2356E-04	3.97562E-05	5.45312E-04
N/H	None	-1.455	0.979	N	0.621	0.293	0.28297238246	gnomAD-2.1.1	5.54E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.14E-05	0
N/H	None	-1.455	0.979	N	0.621	0.293	0.28297238246	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/H	None	-1.455	0.979	N	0.621	0.293	0.28297238246	gnomAD-4.0.0	1.1144E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.49471E-05	0	0
N/S	None	None	0.309	N	0.515	0.097	0.168933306366	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	7.32654E-05
N/Y	rs187868672	-0.654	0.979	N	0.739	0.327	0.430923071578	gnomAD-2.1.1	5.54E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.14E-05	0
N/Y	rs187868672	-0.654	0.979	N	0.739	0.327	0.430923071578	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/Y	rs187868672	-0.654	0.979	N	0.739	0.327	0.430923071578	gnomAD-4.0.0	1.96659E-06	None	None	None	None	N	None	2.77801E-05	0	None	0	0	None	0	0	8.7924E-07	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
N/A	0.3747	ambiguous	0.3538	ambiguous	-1.544	Destabilizing	0.373	N	0.655	neutral	None	None	None	None	N
N/C	0.2971	likely_benign	0.2677	benign	-0.646	Destabilizing	0.996	D	0.758	deleterious	None	None	None	None	N
N/D	0.2957	likely_benign	0.2999	benign	-1.458	Destabilizing	0.684	D	0.547	neutral	N	0.520577744	None	None	N
N/E	0.7534	likely_pathogenic	0.7409	pathogenic	-1.242	Destabilizing	0.854	D	0.628	neutral	None	None	None	None	N
N/F	0.8098	likely_pathogenic	0.7671	pathogenic	-0.958	Destabilizing	0.984	D	0.779	deleterious	None	None	None	None	N
N/G	0.2211	likely_benign	0.2069	benign	-1.935	Destabilizing	0.001	N	0.167	neutral	None	None	None	None	N
N/H	0.1324	likely_benign	0.1249	benign	-1.134	Destabilizing	0.979	D	0.621	neutral	N	0.463473668	None	None	N
N/I	0.7913	likely_pathogenic	0.7509	pathogenic	-0.491	Destabilizing	0.884	D	0.793	deleterious	N	0.473370247	None	None	N
N/K	0.5888	likely_pathogenic	0.5802	pathogenic	-0.339	Destabilizing	0.684	D	0.633	neutral	N	0.48821461	None	None	N
N/L	0.6168	likely_pathogenic	0.5813	pathogenic	-0.491	Destabilizing	0.742	D	0.756	deleterious	None	None	None	None	N
N/M	0.7135	likely_pathogenic	0.6807	pathogenic	-0.241	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	N
N/P	0.9609	likely_pathogenic	0.9585	pathogenic	-0.817	Destabilizing	0.984	D	0.761	deleterious	None	None	None	None	N
N/Q	0.5357	ambiguous	0.5264	ambiguous	-0.967	Destabilizing	0.984	D	0.663	neutral	None	None	None	None	N
N/R	0.5351	ambiguous	0.522	ambiguous	-0.328	Destabilizing	0.953	D	0.673	neutral	None	None	None	None	N
N/S	0.0871	likely_benign	0.0818	benign	-1.345	Destabilizing	0.309	N	0.515	neutral	N	0.446194629	None	None	N
N/T	0.2404	likely_benign	0.227	benign	-0.932	Destabilizing	0.012	N	0.177	neutral	N	0.468418128	None	None	N
N/V	0.7293	likely_pathogenic	0.6901	pathogenic	-0.817	Destabilizing	0.742	D	0.767	deleterious	None	None	None	None	N
N/W	0.9	likely_pathogenic	0.8799	pathogenic	-0.636	Destabilizing	0.996	D	0.767	deleterious	None	None	None	None	N
N/Y	0.3288	likely_benign	0.3051	benign	-0.407	Destabilizing	0.979	D	0.739	prob.delet.	N	0.502165342	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.