TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32356	97291;97292;97293	chr2:178542788;178542787;178542786	chr2:179407515;179407514;179407513
N2AB	30715	92368;92369;92370	chr2:178542788;178542787;178542786	chr2:179407515;179407514;179407513
N2A	29788	89587;89588;89589	chr2:178542788;178542787;178542786	chr2:179407515;179407514;179407513
N2B	23291	70096;70097;70098	chr2:178542788;178542787;178542786	chr2:179407515;179407514;179407513
Novex-1	23416	70471;70472;70473	chr2:178542788;178542787;178542786	chr2:179407515;179407514;179407513
Novex-2	23483	70672;70673;70674	chr2:178542788;178542787;178542786	chr2:179407515;179407514;179407513
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: Ig-154
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.3411
• 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/A	rs368184712	-0.617	0.994	N	0.553	0.471	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/A	rs368184712	-0.617	0.994	N	0.553	0.471	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/A	rs368184712	-0.617	0.994	N	0.553	0.471	None	gnomAD-4.0.0	1.42533E-05	None	None	None	None	N	None	0	0	None	3.37861E-05	0	None	0	0	1.77999E-05	0	1.60118E-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	0.1545	likely_benign	0.1373	benign	-0.546	Destabilizing	0.994	D	0.553	neutral	N	0.48874862	None	None	N
E/C	0.8332	likely_pathogenic	0.7867	pathogenic	-0.111	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/D	0.1555	likely_benign	0.1384	benign	-0.7	Destabilizing	0.104	N	0.159	neutral	N	0.440264026	None	None	N
E/F	0.7338	likely_pathogenic	0.6854	pathogenic	-0.463	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/G	0.2151	likely_benign	0.1793	benign	-0.816	Destabilizing	0.994	D	0.594	neutral	N	0.519591602	None	None	N
E/H	0.414	ambiguous	0.367	ambiguous	-0.681	Destabilizing	1.0	D	0.581	neutral	None	None	None	None	N
E/I	0.3427	ambiguous	0.3072	benign	0.153	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/K	0.1886	likely_benign	0.1658	benign	-0.275	Destabilizing	0.994	D	0.475	neutral	N	0.458983073	None	None	N
E/L	0.437	ambiguous	0.3808	ambiguous	0.153	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/M	0.4354	ambiguous	0.3882	ambiguous	0.503	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/N	0.2815	likely_benign	0.2523	benign	-0.461	Destabilizing	0.998	D	0.567	neutral	None	None	None	None	N
E/P	0.9181	likely_pathogenic	0.9048	pathogenic	-0.059	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/Q	0.1292	likely_benign	0.1167	benign	-0.397	Destabilizing	0.998	D	0.543	neutral	N	0.485959031	None	None	N
E/R	0.2924	likely_benign	0.2603	benign	-0.12	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
E/S	0.1977	likely_benign	0.1786	benign	-0.7	Destabilizing	0.992	D	0.474	neutral	None	None	None	None	N
E/T	0.1858	likely_benign	0.1633	benign	-0.495	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
E/V	0.208	likely_benign	0.1878	benign	-0.059	Destabilizing	0.999	D	0.735	prob.delet.	N	0.486305747	None	None	N
E/W	0.8926	likely_pathogenic	0.8609	pathogenic	-0.366	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/Y	0.6586	likely_pathogenic	0.5959	pathogenic	-0.26	Destabilizing	1.0	D	0.719	prob.delet.	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.