TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3120	9583;9584;9585	chr2:178767872;178767871;178767870	chr2:179632599;179632598;179632597
N2AB	3120	9583;9584;9585	chr2:178767872;178767871;178767870	chr2:179632599;179632598;179632597
N2A	3120	9583;9584;9585	chr2:178767872;178767871;178767870	chr2:179632599;179632598;179632597
N2B	3074	9445;9446;9447	chr2:178767872;178767871;178767870	chr2:179632599;179632598;179632597
Novex-1	3074	9445;9446;9447	chr2:178767872;178767871;178767870	chr2:179632599;179632598;179632597
Novex-2	3074	9445;9446;9447	chr2:178767872;178767871;178767870	chr2:179632599;179632598;179632597
Novex-3	3120	9583;9584;9585	chr2:178767872;178767871;178767870	chr2:179632599;179632598;179632597

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Ig-21
• Domain position: 63
• Structural Position: 145
• Q(SASA): 0.5583
• 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
R/G	None	None	0.956	N	0.587	0.483	0.682070973213	gnomAD-4.0.0	6.84078E-07	None	None	None	None	N	None	0	0	None	3.82614E-05	0	None	0	0	0	0	0
R/L	None	None	0.956	N	0.567	0.459	0.671819145075	gnomAD-4.0.0	6.84078E-07	None	None	None	None	N	None	0	0	None	0	2.5208E-05	None	0	0	0	0	0
R/P	rs72647894	None	0.994	D	0.678	0.522	0.63959863781	gnomAD-4.0.0	6.84078E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99298E-07	0	0
R/Q	rs72647894	0.01	0.994	N	0.563	0.266	None	gnomAD-2.1.1	4.31987E-03	None	None	None	None	N	None	5.60808E-04	6.21293E-04	None	1.15853E-03	0	None	4.47595E-03	None	8.84039E-03	6.11478E-03	3.46741E-03
R/Q	rs72647894	0.01	0.994	N	0.563	0.266	None	gnomAD-3.1.2	3.89788E-03	None	None	None	None	N	None	7.24393E-04	1.17909E-03	1.09649E-03	1.1534E-03	1.9253E-04	None	1.07385E-02	0	5.95291E-03	3.93375E-03	4.79846E-04
R/Q	rs72647894	0.01	0.994	N	0.563	0.266	None	1000 genomes	1.59744E-03	None	None	None	None	N	None	8E-04	0	None	None	0	2E-03	None	None	None	5.1E-03	None
R/Q	rs72647894	0.01	0.994	N	0.563	0.266	None	gnomAD-4.0.0	3.7582E-03	None	None	None	None	N	None	7.73168E-04	8.49887E-04	None	8.7826E-04	2.22955E-05	None	9.02674E-03	2.63939E-03	4.04067E-03	4.09512E-03	3.104E-03
R/W	rs149492487	-0.507	1.0	N	0.797	0.598	None	gnomAD-2.1.1	3.54E-05	None	None	None	None	N	None	1.20173E-04	0	None	0	0	None	1.30685E-04	None	0	2.33E-05	0
R/W	rs149492487	-0.507	1.0	N	0.797	0.598	None	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	1.44844E-04	0	0	0	0	None	0	0	0	0	4.78469E-04
R/W	rs149492487	-0.507	1.0	N	0.797	0.598	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/W	rs149492487	-0.507	1.0	N	0.797	0.598	None	gnomAD-4.0.0	1.42498E-05	None	None	None	None	N	None	1.0663E-04	0	None	0	0	None	0	0	5.08476E-06	7.68673E-05	3.19969E-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
R/A	0.6401	likely_pathogenic	0.7185	pathogenic	-0.474	Destabilizing	0.919	D	0.587	neutral	None	None	None	None	N
R/C	0.4165	ambiguous	0.4207	ambiguous	-0.438	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
R/D	0.908	likely_pathogenic	0.9294	pathogenic	-0.038	Destabilizing	0.851	D	0.565	neutral	None	None	None	None	N
R/E	0.6499	likely_pathogenic	0.7205	pathogenic	0.038	Stabilizing	0.851	D	0.553	neutral	None	None	None	None	N
R/F	0.773	likely_pathogenic	0.8319	pathogenic	-0.606	Destabilizing	0.996	D	0.703	prob.neutral	None	None	None	None	N
R/G	0.5037	ambiguous	0.5709	pathogenic	-0.712	Destabilizing	0.956	D	0.587	neutral	N	0.509097238	None	None	N
R/H	0.1993	likely_benign	0.2024	benign	-1.066	Destabilizing	0.988	D	0.569	neutral	None	None	None	None	N
R/I	0.5639	ambiguous	0.7068	pathogenic	0.138	Stabilizing	0.988	D	0.697	prob.neutral	None	None	None	None	N
R/K	0.1196	likely_benign	0.1489	benign	-0.463	Destabilizing	0.034	N	0.221	neutral	None	None	None	None	N
R/L	0.4567	ambiguous	0.5411	ambiguous	0.138	Stabilizing	0.956	D	0.567	neutral	N	0.50993017	None	None	N
R/M	0.484	ambiguous	0.6237	pathogenic	-0.096	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
R/N	0.8006	likely_pathogenic	0.8476	pathogenic	0.022	Stabilizing	0.132	N	0.313	neutral	None	None	None	None	N
R/P	0.9718	likely_pathogenic	0.976	pathogenic	-0.045	Destabilizing	0.994	D	0.678	prob.neutral	D	0.677368833	None	None	N
R/Q	0.1712	likely_benign	0.1862	benign	-0.208	Destabilizing	0.994	D	0.563	neutral	N	0.503151226	None	None	N
R/S	0.7277	likely_pathogenic	0.7791	pathogenic	-0.617	Destabilizing	0.919	D	0.587	neutral	None	None	None	None	N
R/T	0.4906	ambiguous	0.5859	pathogenic	-0.387	Destabilizing	0.919	D	0.597	neutral	None	None	None	None	N
R/V	0.588	likely_pathogenic	0.6875	pathogenic	-0.045	Destabilizing	0.988	D	0.672	neutral	None	None	None	None	N
R/W	0.4038	ambiguous	0.4704	ambiguous	-0.434	Destabilizing	1.0	D	0.797	deleterious	N	0.507171231	None	None	N
R/Y	0.6703	likely_pathogenic	0.7226	pathogenic	-0.074	Destabilizing	0.996	D	0.689	prob.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.