TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31998	96217;96218;96219	chr2:178544237;178544236;178544235	chr2:179408964;179408963;179408962
N2AB	30357	91294;91295;91296	chr2:178544237;178544236;178544235	chr2:179408964;179408963;179408962
N2A	29430	88513;88514;88515	chr2:178544237;178544236;178544235	chr2:179408964;179408963;179408962
N2B	22933	69022;69023;69024	chr2:178544237;178544236;178544235	chr2:179408964;179408963;179408962
Novex-1	23058	69397;69398;69399	chr2:178544237;178544236;178544235	chr2:179408964;179408963;179408962
Novex-2	23125	69598;69599;69600	chr2:178544237;178544236;178544235	chr2:179408964;179408963;179408962
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: Fn3-121
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.7894
• Predicted PPI site: I

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	rs1181902339	-0.089	0.996	N	0.718	0.332	0.377451072189	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/A	rs1181902339	-0.089	0.996	N	0.718	0.332	0.377451072189	gnomAD-4.0.0	3.18339E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71916E-06	0	0
E/K	rs775585263	0.869	0.999	N	0.698	0.302	0.33440975612	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/K	rs775585263	0.869	0.999	N	0.698	0.302	0.33440975612	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	1.92753E-04	None	0	0	1.47E-05	2.06954E-04	0
E/K	rs775585263	0.869	0.999	N	0.698	0.302	0.33440975612	gnomAD-4.0.0	1.73542E-05	None	None	None	None	I	None	0	0	None	0	4.45653E-05	None	0	0	1.78028E-05	4.39203E-05	1.60128E-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	0.1331	likely_benign	0.1342	benign	-0.009	Destabilizing	0.996	D	0.718	prob.delet.	N	0.484347585	None	None	I
E/C	0.7096	likely_pathogenic	0.7407	pathogenic	0.104	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
E/D	0.089	likely_benign	0.1005	benign	-0.206	Destabilizing	0.262	N	0.277	neutral	N	0.451080374	None	None	I
E/F	0.6355	likely_pathogenic	0.6507	pathogenic	-0.109	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/G	0.1435	likely_benign	0.141	benign	-0.12	Destabilizing	0.999	D	0.637	neutral	N	0.503645422	None	None	I
E/H	0.375	ambiguous	0.3826	ambiguous	0.332	Stabilizing	1.0	D	0.699	prob.delet.	None	None	None	None	I
E/I	0.3128	likely_benign	0.3115	benign	0.221	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
E/K	0.1332	likely_benign	0.1281	benign	0.599	Stabilizing	0.999	D	0.698	prob.delet.	N	0.511995547	None	None	I
E/L	0.329	likely_benign	0.3336	benign	0.221	Stabilizing	1.0	D	0.734	deleterious	None	None	None	None	I
E/M	0.4043	ambiguous	0.4094	ambiguous	0.169	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
E/N	0.1731	likely_benign	0.1887	benign	0.399	Stabilizing	0.998	D	0.738	deleterious	None	None	None	None	I
E/P	0.2974	likely_benign	0.3379	benign	0.162	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
E/Q	0.1369	likely_benign	0.1371	benign	0.405	Stabilizing	1.0	D	0.733	deleterious	N	0.496468734	None	None	I
E/R	0.2357	likely_benign	0.2321	benign	0.693	Stabilizing	0.999	D	0.764	deleterious	None	None	None	None	I
E/S	0.1469	likely_benign	0.1534	benign	0.27	Stabilizing	0.993	D	0.683	prob.neutral	None	None	None	None	I
E/T	0.1706	likely_benign	0.178	benign	0.369	Stabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
E/V	0.1895	likely_benign	0.1865	benign	0.162	Stabilizing	1.0	D	0.751	deleterious	N	0.496604807	None	None	I
E/W	0.8558	likely_pathogenic	0.8605	pathogenic	-0.079	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
E/Y	0.5093	ambiguous	0.5255	ambiguous	0.115	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	I

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.