TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20019	60280;60281;60282	chr2:178591764;178591763;178591762	chr2:179456491;179456490;179456489
N2AB	18378	55357;55358;55359	chr2:178591764;178591763;178591762	chr2:179456491;179456490;179456489
N2A	17451	52576;52577;52578	chr2:178591764;178591763;178591762	chr2:179456491;179456490;179456489
N2B	10954	33085;33086;33087	chr2:178591764;178591763;178591762	chr2:179456491;179456490;179456489
Novex-1	11079	33460;33461;33462	chr2:178591764;178591763;178591762	chr2:179456491;179456490;179456489
Novex-2	11146	33661;33662;33663	chr2:178591764;178591763;178591762	chr2:179456491;179456490;179456489
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: Fn3-33
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.6473
• 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	None	None	0.645	N	0.638	0.316	0.430694319191	gnomAD-4.0.0	6.8439E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15958E-05	0
E/D	rs1342395614	None	0.002	N	0.278	0.064	0.0954503805726	gnomAD-4.0.0	6.84391E-06	None	None	None	None	N	None	0	2.23784E-05	None	0	0	None	0	0	7.19695E-06	0	1.657E-05
E/G	rs1301342171	None	0.645	N	0.587	0.293	0.464953486513	gnomAD-4.0.0	6.8439E-06	None	None	None	None	N	None	0	2.23784E-05	None	0	0	None	0	0	5.39764E-06	2.31916E-05	1.65706E-05
E/K	rs201487340	0.19	0.645	N	0.605	0.267	None	gnomAD-2.1.1	1.49528E-03	None	None	None	None	N	None	1.57982E-02	7.36961E-04	None	0	0	None	3.27E-05	None	0	3.92E-05	5.62746E-04
E/K	rs201487340	0.19	0.645	N	0.605	0.267	None	gnomAD-3.1.2	4.11157E-03	None	None	None	None	N	None	1.45333E-02	9.84252E-04	0	0	0	None	0	0	2.94E-05	0	2.87081E-03
E/K	rs201487340	0.19	0.645	N	0.605	0.267	None	1000 genomes	1.79712E-03	None	None	None	None	N	None	6.8E-03	0	None	None	0	0	None	None	None	0	None
E/K	rs201487340	0.19	0.645	N	0.605	0.267	None	gnomAD-4.0.0	7.9093E-04	None	None	None	None	N	None	1.54946E-02	7.00631E-04	None	0	0	None	0	1.65125E-04	1.1021E-05	2.19626E-05	8.96603E-04

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	0.1376	likely_benign	0.1129	benign	-0.66	Destabilizing	0.645	D	0.638	neutral	N	0.4752481	None	None	N
E/C	0.8758	likely_pathogenic	0.8578	pathogenic	-0.268	Destabilizing	0.995	D	0.704	prob.neutral	None	None	None	None	N
E/D	0.1308	likely_benign	0.1036	benign	-0.844	Destabilizing	0.002	N	0.278	neutral	N	0.478557764	None	None	N
E/F	0.7835	likely_pathogenic	0.7224	pathogenic	-0.448	Destabilizing	0.995	D	0.678	prob.neutral	None	None	None	None	N
E/G	0.2446	likely_benign	0.1904	benign	-0.939	Destabilizing	0.645	D	0.587	neutral	N	0.481118066	None	None	N
E/H	0.5953	likely_pathogenic	0.5208	ambiguous	-0.595	Destabilizing	0.995	D	0.587	neutral	None	None	None	None	N
E/I	0.3217	likely_benign	0.2686	benign	0.07	Stabilizing	0.945	D	0.699	prob.neutral	None	None	None	None	N
E/K	0.2648	likely_benign	0.2044	benign	-0.291	Destabilizing	0.645	D	0.605	neutral	N	0.418528025	None	None	N
E/L	0.4183	ambiguous	0.3482	ambiguous	0.07	Stabilizing	0.945	D	0.693	prob.neutral	None	None	None	None	N
E/M	0.4811	ambiguous	0.4173	ambiguous	0.367	Stabilizing	0.995	D	0.666	neutral	None	None	None	None	N
E/N	0.2863	likely_benign	0.2217	benign	-0.591	Destabilizing	0.809	D	0.592	neutral	None	None	None	None	N
E/P	0.594	likely_pathogenic	0.5245	ambiguous	-0.152	Destabilizing	0.945	D	0.633	neutral	None	None	None	None	N
E/Q	0.2377	likely_benign	0.207	benign	-0.532	Destabilizing	0.864	D	0.551	neutral	N	0.508899313	None	None	N
E/R	0.4512	ambiguous	0.3975	ambiguous	-0.075	Destabilizing	0.894	D	0.623	neutral	None	None	None	None	N
E/S	0.2537	likely_benign	0.1999	benign	-0.815	Destabilizing	0.547	D	0.607	neutral	None	None	None	None	N
E/T	0.2582	likely_benign	0.2054	benign	-0.597	Destabilizing	0.894	D	0.591	neutral	None	None	None	None	N
E/V	0.1939	likely_benign	0.1613	benign	-0.152	Destabilizing	0.928	D	0.668	neutral	N	0.444021116	None	None	N
E/W	0.9239	likely_pathogenic	0.9035	pathogenic	-0.28	Destabilizing	0.995	D	0.703	prob.neutral	None	None	None	None	N
E/Y	0.6553	likely_pathogenic	0.5828	pathogenic	-0.219	Destabilizing	0.995	D	0.661	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.