TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27178	81757;81758;81759	chr2:178564600;178564599;178564598	chr2:179429327;179429326;179429325
N2AB	25537	76834;76835;76836	chr2:178564600;178564599;178564598	chr2:179429327;179429326;179429325
N2A	24610	74053;74054;74055	chr2:178564600;178564599;178564598	chr2:179429327;179429326;179429325
N2B	18113	54562;54563;54564	chr2:178564600;178564599;178564598	chr2:179429327;179429326;179429325
Novex-1	18238	54937;54938;54939	chr2:178564600;178564599;178564598	chr2:179429327;179429326;179429325
Novex-2	18305	55138;55139;55140	chr2:178564600;178564599;178564598	chr2:179429327;179429326;179429325
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: Fn3-86
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6884
• 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/K	rs397517721	None	0.977	N	0.615	0.33	0.318540980066	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	1.31027E-04	0	0	0	None	0	0	0	0	0
E/K	rs397517721	None	0.977	N	0.615	0.33	0.318540980066	gnomAD-4.0.0	1.31518E-05	None	None	None	None	N	None	0	1.31027E-04	None	0	0	None	0	0	0	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
E/A	0.3344	likely_benign	0.2893	benign	-0.582	Destabilizing	0.977	D	0.709	prob.delet.	N	0.483623689	None	None	N
E/C	0.922	likely_pathogenic	0.9034	pathogenic	-0.277	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/D	0.2022	likely_benign	0.1758	benign	-0.675	Destabilizing	0.117	N	0.237	neutral	N	0.483877179	None	None	N
E/F	0.8614	likely_pathogenic	0.8165	pathogenic	-0.125	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/G	0.5135	ambiguous	0.453	ambiguous	-0.877	Destabilizing	0.993	D	0.747	deleterious	N	0.497715473	None	None	N
E/H	0.659	likely_pathogenic	0.5994	pathogenic	-0.135	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/I	0.3917	ambiguous	0.3481	ambiguous	0.197	Stabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
E/K	0.2794	likely_benign	0.242	benign	-0.068	Destabilizing	0.977	D	0.615	neutral	N	0.509800603	None	None	N
E/L	0.5725	likely_pathogenic	0.5137	ambiguous	0.197	Stabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
E/M	0.602	likely_pathogenic	0.5457	ambiguous	0.363	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/N	0.4436	ambiguous	0.3752	ambiguous	-0.547	Destabilizing	0.99	D	0.76	deleterious	None	None	None	None	N
E/P	0.9787	likely_pathogenic	0.9703	pathogenic	-0.041	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
E/Q	0.2249	likely_benign	0.2085	benign	-0.455	Destabilizing	0.997	D	0.709	prob.delet.	D	0.522423184	None	None	N
E/R	0.4499	ambiguous	0.397	ambiguous	0.222	Stabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
E/S	0.3783	ambiguous	0.3272	benign	-0.754	Destabilizing	0.983	D	0.66	neutral	None	None	None	None	N
E/T	0.3409	ambiguous	0.2978	benign	-0.511	Destabilizing	0.995	D	0.809	deleterious	None	None	None	None	N
E/V	0.2367	likely_benign	0.2052	benign	-0.041	Destabilizing	0.997	D	0.814	deleterious	D	0.522924616	None	None	N
E/W	0.9595	likely_pathogenic	0.944	pathogenic	0.121	Stabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
E/Y	0.8009	likely_pathogenic	0.7411	pathogenic	0.135	Stabilizing	1.0	D	0.817	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.