TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26779	80560;80561;80562	chr2:178565797;178565796;178565795	chr2:179430524;179430523;179430522
N2AB	25138	75637;75638;75639	chr2:178565797;178565796;178565795	chr2:179430524;179430523;179430522
N2A	24211	72856;72857;72858	chr2:178565797;178565796;178565795	chr2:179430524;179430523;179430522
N2B	17714	53365;53366;53367	chr2:178565797;178565796;178565795	chr2:179430524;179430523;179430522
Novex-1	17839	53740;53741;53742	chr2:178565797;178565796;178565795	chr2:179430524;179430523;179430522
Novex-2	17906	53941;53942;53943	chr2:178565797;178565796;178565795	chr2:179430524;179430523;179430522
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: Fn3-82
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.8342
• 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/D	rs760599182	-0.12	None	N	0.361	0.033	0.223847106136	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs760599182	-0.12	None	N	0.361	0.033	0.223847106136	gnomAD-4.0.0	6.36647E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73115E-05	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
E/A	0.3332	likely_benign	0.3239	benign	-0.49	Destabilizing	0.581	D	0.649	prob.neutral	N	0.509008383	None	None	N
E/C	0.9227	likely_pathogenic	0.9328	pathogenic	-0.206	Destabilizing	0.993	D	0.767	deleterious	None	None	None	None	N
E/D	0.2593	likely_benign	0.3174	benign	-0.502	Destabilizing	None	N	0.361	neutral	N	0.467759193	None	None	N
E/F	0.9025	likely_pathogenic	0.9197	pathogenic	-0.308	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	N
E/G	0.4175	ambiguous	0.349	ambiguous	-0.711	Destabilizing	0.822	D	0.399	neutral	N	0.518110655	None	None	N
E/H	0.8319	likely_pathogenic	0.8496	pathogenic	-0.149	Destabilizing	0.995	D	0.571	neutral	None	None	None	None	N
E/I	0.7152	likely_pathogenic	0.7838	pathogenic	0.068	Stabilizing	0.919	D	0.689	prob.delet.	None	None	None	None	N
E/K	0.5654	likely_pathogenic	0.5676	pathogenic	0.045	Stabilizing	0.72	D	0.625	neutral	N	0.479011653	None	None	N
E/L	0.6708	likely_pathogenic	0.7321	pathogenic	0.068	Stabilizing	0.919	D	0.689	prob.delet.	None	None	None	None	N
E/M	0.6356	likely_pathogenic	0.6743	pathogenic	0.157	Stabilizing	0.959	D	0.638	neutral	None	None	None	None	N
E/N	0.5322	ambiguous	0.5684	pathogenic	-0.252	Destabilizing	0.565	D	0.59	neutral	None	None	None	None	N
E/P	0.985	likely_pathogenic	0.9875	pathogenic	-0.097	Destabilizing	0.628	D	0.573	neutral	None	None	None	None	N
E/Q	0.2396	likely_benign	0.2276	benign	-0.213	Destabilizing	0.929	D	0.531	neutral	N	0.468478268	None	None	N
E/R	0.7165	likely_pathogenic	0.7179	pathogenic	0.305	Stabilizing	0.96	D	0.621	neutral	None	None	None	None	N
E/S	0.3516	ambiguous	0.3526	ambiguous	-0.433	Destabilizing	0.648	D	0.632	neutral	None	None	None	None	N
E/T	0.5279	ambiguous	0.5807	pathogenic	-0.259	Destabilizing	0.899	D	0.565	neutral	None	None	None	None	N
E/V	0.4857	ambiguous	0.5589	ambiguous	-0.097	Destabilizing	0.859	D	0.604	neutral	N	0.487151954	None	None	N
E/W	0.9796	likely_pathogenic	0.984	pathogenic	-0.141	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/Y	0.8787	likely_pathogenic	0.8966	pathogenic	-0.073	Destabilizing	0.999	D	0.559	neutral	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.