TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26417	79474;79475;79476	chr2:178566883;178566882;178566881	chr2:179431610;179431609;179431608
N2AB	24776	74551;74552;74553	chr2:178566883;178566882;178566881	chr2:179431610;179431609;179431608
N2A	23849	71770;71771;71772	chr2:178566883;178566882;178566881	chr2:179431610;179431609;179431608
N2B	17352	52279;52280;52281	chr2:178566883;178566882;178566881	chr2:179431610;179431609;179431608
Novex-1	17477	52654;52655;52656	chr2:178566883;178566882;178566881	chr2:179431610;179431609;179431608
Novex-2	17544	52855;52856;52857	chr2:178566883;178566882;178566881	chr2:179431610;179431609;179431608
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: Fn3-80
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7035
• 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	rs369019463	0.084	0.014	N	0.192	0.034	0.170165803431	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.24E-05	0
E/D	rs369019463	0.084	0.014	N	0.192	0.034	0.170165803431	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	4.41E-05	0	0
E/D	rs369019463	0.084	0.014	N	0.192	0.034	0.170165803431	gnomAD-4.0.0	8.67713E-05	None	None	None	None	I	None	4.00588E-05	0	None	0	0	None	0	0	1.14439E-04	0	3.20307E-05
E/Q	None	None	0.942	N	0.546	0.262	0.238096912614	gnomAD-4.0.0	2.05291E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.7337E-04	8.99549E-07	0	1.657E-05

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	0.2674	likely_benign	0.2736	benign	-0.353	Destabilizing	0.489	N	0.625	neutral	N	0.491527061	None	None	I
E/C	0.93	likely_pathogenic	0.9301	pathogenic	-0.11	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	I
E/D	0.0971	likely_benign	0.1062	benign	-0.311	Destabilizing	0.014	N	0.192	neutral	N	0.513902488	None	None	I
E/F	0.934	likely_pathogenic	0.9371	pathogenic	-0.199	Destabilizing	0.978	D	0.703	prob.neutral	None	None	None	None	I
E/G	0.34	likely_benign	0.3487	ambiguous	-0.544	Destabilizing	0.698	D	0.639	neutral	N	0.475651653	None	None	I
E/H	0.7271	likely_pathogenic	0.7397	pathogenic	0.134	Stabilizing	0.998	D	0.549	neutral	None	None	None	None	I
E/I	0.6608	likely_pathogenic	0.6862	pathogenic	0.117	Stabilizing	0.956	D	0.711	prob.delet.	None	None	None	None	I
E/K	0.3868	ambiguous	0.4136	ambiguous	0.317	Stabilizing	0.822	D	0.59	neutral	N	0.506091082	None	None	I
E/L	0.6857	likely_pathogenic	0.6966	pathogenic	0.117	Stabilizing	0.956	D	0.626	neutral	None	None	None	None	I
E/M	0.7265	likely_pathogenic	0.7383	pathogenic	0.139	Stabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	I
E/N	0.3534	ambiguous	0.3648	ambiguous	-0.026	Destabilizing	0.86	D	0.57	neutral	None	None	None	None	I
E/P	0.4208	ambiguous	0.4362	ambiguous	-0.02	Destabilizing	0.978	D	0.634	neutral	None	None	None	None	I
E/Q	0.2895	likely_benign	0.2883	benign	0.014	Stabilizing	0.942	D	0.546	neutral	N	0.509208745	None	None	I
E/R	0.5671	likely_pathogenic	0.5776	pathogenic	0.568	Stabilizing	0.956	D	0.565	neutral	None	None	None	None	I
E/S	0.3158	likely_benign	0.3172	benign	-0.189	Destabilizing	0.076	N	0.313	neutral	None	None	None	None	I
E/T	0.4046	ambiguous	0.4195	ambiguous	-0.029	Destabilizing	0.076	N	0.37	neutral	None	None	None	None	I
E/V	0.4329	ambiguous	0.4568	ambiguous	-0.02	Destabilizing	0.942	D	0.605	neutral	N	0.4882225	None	None	I
E/W	0.9799	likely_pathogenic	0.9805	pathogenic	-0.042	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	I
E/Y	0.868	likely_pathogenic	0.8742	pathogenic	0.047	Stabilizing	0.993	D	0.695	prob.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.