TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18958	57097;57098;57099	chr2:178598838;178598837;178598836	chr2:179463565;179463564;179463563
N2AB	17317	52174;52175;52176	chr2:178598838;178598837;178598836	chr2:179463565;179463564;179463563
N2A	16390	49393;49394;49395	chr2:178598838;178598837;178598836	chr2:179463565;179463564;179463563
N2B	9893	29902;29903;29904	chr2:178598838;178598837;178598836	chr2:179463565;179463564;179463563
Novex-1	10018	30277;30278;30279	chr2:178598838;178598837;178598836	chr2:179463565;179463564;179463563
Novex-2	10085	30478;30479;30480	chr2:178598838;178598837;178598836	chr2:179463565;179463564;179463563
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-25
• Domain position: 75
• Structural Position: 103
• Q(SASA): 0.251
• 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
D/E	None	None	0.002	N	0.11	0.078	0.136095386433	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
D/H	rs576158850	-0.96	0.97	N	0.539	0.3	0.307966526162	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
D/H	rs576158850	-0.96	0.97	N	0.539	0.3	0.307966526162	gnomAD-4.0.0	6.84403E-07	None	None	None	None	N	None	0	0	None	0	2.52372E-05	None	0	0	0	0	0
D/N	rs576158850	-0.322	0.91	N	0.479	0.197	None	gnomAD-2.1.1	4.43E-05	None	None	None	None	N	None	0	2.9E-05	None	0	2.79611E-04	None	0	None	0	4.46E-05	0
D/N	rs576158850	-0.322	0.91	N	0.479	0.197	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	4.83E-05	6.56E-05	0	0	0	None	0	0	7.36E-05	2.07297E-04	0
D/N	rs576158850	-0.322	0.91	N	0.479	0.197	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
D/N	rs576158850	-0.322	0.91	N	0.479	0.197	None	gnomAD-4.0.0	5.64075E-05	None	None	None	None	N	None	5.33518E-05	1.66756E-05	None	0	1.11717E-04	None	1.56226E-05	0	6.35871E-05	3.29497E-05	3.20195E-05
D/V	rs2052516508	None	0.023	N	0.419	0.259	0.348983352498	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/V	rs2052516508	None	0.023	N	0.419	0.259	0.348983352498	gnomAD-4.0.0	6.57843E-06	None	None	None	None	N	None	2.41418E-05	0	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
D/A	0.1749	likely_benign	0.1819	benign	-0.268	Destabilizing	0.425	N	0.448	neutral	N	0.435652348	None	None	N
D/C	0.5743	likely_pathogenic	0.6024	pathogenic	-0.053	Destabilizing	0.995	D	0.619	neutral	None	None	None	None	N
D/E	0.1197	likely_benign	0.1266	benign	-0.8	Destabilizing	0.002	N	0.11	neutral	N	0.347107857	None	None	N
D/F	0.5726	likely_pathogenic	0.5818	pathogenic	-0.608	Destabilizing	0.893	D	0.607	neutral	None	None	None	None	N
D/G	0.2948	likely_benign	0.3098	benign	-0.554	Destabilizing	0.642	D	0.476	neutral	N	0.460953438	None	None	N
D/H	0.2939	likely_benign	0.2878	benign	-1.031	Destabilizing	0.97	D	0.539	neutral	N	0.479712557	None	None	N
D/I	0.2574	likely_benign	0.246	benign	0.459	Stabilizing	0.031	N	0.461	neutral	None	None	None	None	N
D/K	0.3762	ambiguous	0.3656	ambiguous	-0.284	Destabilizing	0.543	D	0.472	neutral	None	None	None	None	N
D/L	0.3371	likely_benign	0.3364	benign	0.459	Stabilizing	0.329	N	0.467	neutral	None	None	None	None	N
D/M	0.4911	ambiguous	0.5103	ambiguous	0.95	Stabilizing	0.176	N	0.417	neutral	None	None	None	None	N
D/N	0.0975	likely_benign	0.1103	benign	-0.517	Destabilizing	0.91	D	0.479	neutral	N	0.443501041	None	None	N
D/P	0.739	likely_pathogenic	0.7371	pathogenic	0.242	Stabilizing	0.944	D	0.543	neutral	None	None	None	None	N
D/Q	0.2669	likely_benign	0.2652	benign	-0.426	Destabilizing	0.543	D	0.492	neutral	None	None	None	None	N
D/R	0.4164	ambiguous	0.3982	ambiguous	-0.396	Destabilizing	0.893	D	0.579	neutral	None	None	None	None	N
D/S	0.1191	likely_benign	0.1267	benign	-0.755	Destabilizing	0.329	N	0.401	neutral	None	None	None	None	N
D/T	0.1774	likely_benign	0.1842	benign	-0.522	Destabilizing	0.031	N	0.255	neutral	None	None	None	None	N
D/V	0.1594	likely_benign	0.156	benign	0.242	Stabilizing	0.023	N	0.419	neutral	N	0.426648863	None	None	N
D/W	0.8868	likely_pathogenic	0.8922	pathogenic	-0.716	Destabilizing	0.995	D	0.65	neutral	None	None	None	None	N
D/Y	0.2676	likely_benign	0.2719	benign	-0.434	Destabilizing	0.99	D	0.617	neutral	N	0.471074431	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.