TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30197	90814;90815;90816	chr2:178552311;178552310;178552309	chr2:179417038;179417037;179417036
N2AB	28556	85891;85892;85893	chr2:178552311;178552310;178552309	chr2:179417038;179417037;179417036
N2A	27629	83110;83111;83112	chr2:178552311;178552310;178552309	chr2:179417038;179417037;179417036
N2B	21132	63619;63620;63621	chr2:178552311;178552310;178552309	chr2:179417038;179417037;179417036
Novex-1	21257	63994;63995;63996	chr2:178552311;178552310;178552309	chr2:179417038;179417037;179417036
Novex-2	21324	64195;64196;64197	chr2:178552311;178552310;178552309	chr2:179417038;179417037;179417036
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: Ig-148
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.7279
• 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
E/G	rs531923761	-0.518	0.993	N	0.65	0.432	0.32082282376	gnomAD-2.1.1	3.24E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.33707E-04	None	0	0	1.67504E-04
E/G	rs531923761	-0.518	0.993	N	0.65	0.432	0.32082282376	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
E/G	rs531923761	-0.518	0.993	N	0.65	0.432	0.32082282376	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/G	rs531923761	-0.518	0.993	N	0.65	0.432	0.32082282376	gnomAD-4.0.0	1.02693E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	9.44644E-05	2.84722E-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	0.1448	likely_benign	0.1526	benign	-0.316	Destabilizing	0.977	D	0.625	neutral	N	0.510717749	None	None	N
E/C	0.7779	likely_pathogenic	0.7998	pathogenic	-0.183	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/D	0.1035	likely_benign	0.1111	benign	-0.217	Destabilizing	0.977	D	0.485	neutral	N	0.491438555	None	None	N
E/F	0.7335	likely_pathogenic	0.7507	pathogenic	-0.2	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/G	0.1878	likely_benign	0.2005	benign	-0.495	Destabilizing	0.993	D	0.65	neutral	N	0.512680619	None	None	N
E/H	0.5173	ambiguous	0.5371	ambiguous	0.221	Stabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/I	0.2571	likely_benign	0.2783	benign	0.119	Stabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
E/K	0.2841	likely_benign	0.2767	benign	0.21	Stabilizing	0.955	D	0.563	neutral	N	0.497057806	None	None	N
E/L	0.4144	ambiguous	0.4462	ambiguous	0.119	Stabilizing	0.995	D	0.735	prob.delet.	None	None	None	None	N
E/M	0.4652	ambiguous	0.4831	ambiguous	0.062	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
E/N	0.2641	likely_benign	0.2801	benign	-0.013	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	N
E/P	0.5165	ambiguous	0.5466	ambiguous	-0.007	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
E/Q	0.1904	likely_benign	0.1995	benign	0.021	Stabilizing	0.568	D	0.323	neutral	N	0.501714264	None	None	N
E/R	0.4225	ambiguous	0.4099	ambiguous	0.512	Stabilizing	0.99	D	0.723	prob.delet.	None	None	None	None	N
E/S	0.2027	likely_benign	0.2074	benign	-0.219	Destabilizing	0.983	D	0.627	neutral	None	None	None	None	N
E/T	0.2115	likely_benign	0.2265	benign	-0.073	Destabilizing	0.995	D	0.703	prob.neutral	None	None	None	None	N
E/V	0.1755	likely_benign	0.1944	benign	-0.007	Destabilizing	0.997	D	0.723	prob.delet.	N	0.512008615	None	None	N
E/W	0.8757	likely_pathogenic	0.8809	pathogenic	-0.069	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/Y	0.6022	likely_pathogenic	0.6234	pathogenic	0.035	Stabilizing	0.999	D	0.743	deleterious	None	None	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.