TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27941	84046;84047;84048	chr2:178562311;178562310;178562309	chr2:179427038;179427037;179427036
N2AB	26300	79123;79124;79125	chr2:178562311;178562310;178562309	chr2:179427038;179427037;179427036
N2A	25373	76342;76343;76344	chr2:178562311;178562310;178562309	chr2:179427038;179427037;179427036
N2B	18876	56851;56852;56853	chr2:178562311;178562310;178562309	chr2:179427038;179427037;179427036
Novex-1	19001	57226;57227;57228	chr2:178562311;178562310;178562309	chr2:179427038;179427037;179427036
Novex-2	19068	57427;57428;57429	chr2:178562311;178562310;178562309	chr2:179427038;179427037;179427036
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: Fn3-91
• Domain position: 79
• Structural Position: 113
• Q(SASA): 0.6727
• 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	rs545954394	0.878	0.992	N	0.466	0.355	0.36453787251	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	0	5.81E-05	None	0	0	None	0	None	0	3.57E-05	0
E/K	rs545954394	0.878	0.992	N	0.466	0.355	0.36453787251	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	2.41E-05	1.96567E-04	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs545954394	0.878	0.992	N	0.466	0.355	0.36453787251	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
E/K	rs545954394	0.878	0.992	N	0.466	0.355	0.36453787251	gnomAD-4.0.0	3.78119E-05	None	None	None	None	N	None	1.33301E-05	8.33973E-05	None	0	0	None	0	0	4.15389E-05	0	9.60676E-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
E/A	0.303	likely_benign	0.4316	ambiguous	-0.11	Destabilizing	0.958	D	0.515	neutral	N	0.475997461	None	None	N
E/C	0.9365	likely_pathogenic	0.9689	pathogenic	0.105	Stabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
E/D	0.1452	likely_benign	0.1951	benign	-0.211	Destabilizing	0.002	N	0.233	neutral	N	0.448408215	None	None	N
E/F	0.9271	likely_pathogenic	0.9645	pathogenic	-0.17	Destabilizing	0.998	D	0.602	neutral	None	None	None	None	N
E/G	0.2879	likely_benign	0.4018	ambiguous	-0.246	Destabilizing	0.974	D	0.531	neutral	N	0.479629625	None	None	N
E/H	0.735	likely_pathogenic	0.8269	pathogenic	0.213	Stabilizing	0.998	D	0.409	neutral	None	None	None	None	N
E/I	0.5782	likely_pathogenic	0.7455	pathogenic	0.193	Stabilizing	0.996	D	0.609	neutral	None	None	None	None	N
E/K	0.3667	ambiguous	0.4785	ambiguous	0.591	Stabilizing	0.992	D	0.466	neutral	N	0.488638684	None	None	N
E/L	0.6408	likely_pathogenic	0.7894	pathogenic	0.193	Stabilizing	0.989	D	0.591	neutral	None	None	None	None	N
E/M	0.7038	likely_pathogenic	0.8257	pathogenic	0.184	Stabilizing	0.995	D	0.597	neutral	None	None	None	None	N
E/N	0.4457	ambiguous	0.6015	pathogenic	0.354	Stabilizing	0.857	D	0.433	neutral	None	None	None	None	N
E/P	0.8317	likely_pathogenic	0.8785	pathogenic	0.111	Stabilizing	0.976	D	0.483	neutral	None	None	None	None	N
E/Q	0.2534	likely_benign	0.3349	benign	0.362	Stabilizing	0.987	D	0.401	neutral	N	0.517537439	None	None	N
E/R	0.5439	ambiguous	0.6604	pathogenic	0.71	Stabilizing	0.995	D	0.428	neutral	None	None	None	None	N
E/S	0.3342	likely_benign	0.4687	ambiguous	0.215	Stabilizing	0.937	D	0.452	neutral	None	None	None	None	N
E/T	0.4343	ambiguous	0.5858	pathogenic	0.331	Stabilizing	0.976	D	0.473	neutral	None	None	None	None	N
E/V	0.3996	ambiguous	0.5627	ambiguous	0.111	Stabilizing	0.993	D	0.521	neutral	N	0.516806721	None	None	N
E/W	0.9733	likely_pathogenic	0.986	pathogenic	-0.105	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/Y	0.8567	likely_pathogenic	0.9241	pathogenic	0.064	Stabilizing	0.999	D	0.576	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.