TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30707	92344;92345;92346	chr2:178549603;178549602;178549601	chr2:179414330;179414329;179414328
N2AB	29066	87421;87422;87423	chr2:178549603;178549602;178549601	chr2:179414330;179414329;179414328
N2A	28139	84640;84641;84642	chr2:178549603;178549602;178549601	chr2:179414330;179414329;179414328
N2B	21642	65149;65150;65151	chr2:178549603;178549602;178549601	chr2:179414330;179414329;179414328
Novex-1	21767	65524;65525;65526	chr2:178549603;178549602;178549601	chr2:179414330;179414329;179414328
Novex-2	21834	65725;65726;65727	chr2:178549603;178549602;178549601	chr2:179414330;179414329;179414328
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-111
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.4724
• 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/A	rs778868795	-0.208	0.104	N	0.575	0.189	0.29527378943	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.8E-05	0
D/A	rs778868795	-0.208	0.104	N	0.575	0.189	0.29527378943	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
D/A	rs778868795	-0.208	0.104	N	0.575	0.189	0.29527378943	gnomAD-4.0.0	2.23126E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.96725E-05	0	1.60138E-05
D/G	rs778868795	-0.748	0.189	N	0.519	0.199	0.270447802918	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.01E-06	0
D/G	rs778868795	-0.748	0.189	N	0.519	0.199	0.270447802918	gnomAD-4.0.0	6.84361E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99679E-07	0	0
D/N	rs758300381	-0.883	0.189	N	0.529	0.167	0.243398259712	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	0	0	None	0	1.53704E-04	None	0	None	0	0	0
D/N	rs758300381	-0.883	0.189	N	0.529	0.167	0.243398259712	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92456E-04	None	0	0	0	0	0
D/N	rs758300381	-0.883	0.189	N	0.529	0.167	0.243398259712	gnomAD-4.0.0	3.84449E-06	None	None	None	None	N	None	0	0	None	0	7.27273E-05	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	0.2172	likely_benign	0.2067	benign	-0.4	Destabilizing	0.104	N	0.575	neutral	N	0.452918318	None	None	N
D/C	0.6285	likely_pathogenic	0.5866	pathogenic	-0.232	Destabilizing	0.962	D	0.686	prob.delet.	None	None	None	None	N
D/E	0.1096	likely_benign	0.0986	benign	-0.598	Destabilizing	None	N	0.257	neutral	N	0.34507599	None	None	N
D/F	0.5443	ambiguous	0.5172	ambiguous	0.272	Stabilizing	0.87	D	0.715	prob.delet.	None	None	None	None	N
D/G	0.363	ambiguous	0.3473	ambiguous	-0.792	Destabilizing	0.189	N	0.519	neutral	N	0.506310086	None	None	N
D/H	0.3983	ambiguous	0.3588	ambiguous	-0.017	Destabilizing	0.862	D	0.537	neutral	N	0.481529072	None	None	N
D/I	0.26	likely_benign	0.2342	benign	0.645	Stabilizing	0.687	D	0.721	deleterious	None	None	None	None	N
D/K	0.5365	ambiguous	0.4928	ambiguous	-0.35	Destabilizing	0.134	N	0.481	neutral	None	None	None	None	N
D/L	0.3065	likely_benign	0.2701	benign	0.645	Stabilizing	0.519	D	0.7	prob.delet.	None	None	None	None	N
D/M	0.5245	ambiguous	0.4959	ambiguous	0.988	Stabilizing	0.962	D	0.722	deleterious	None	None	None	None	N
D/N	0.1578	likely_benign	0.1444	benign	-0.916	Destabilizing	0.189	N	0.529	neutral	N	0.510638471	None	None	N
D/P	0.7289	likely_pathogenic	0.6632	pathogenic	0.323	Stabilizing	0.687	D	0.5	neutral	None	None	None	None	N
D/Q	0.3723	ambiguous	0.3339	benign	-0.725	Destabilizing	0.351	N	0.494	neutral	None	None	None	None	N
D/R	0.5949	likely_pathogenic	0.5647	pathogenic	-0.115	Destabilizing	0.351	N	0.65	prob.neutral	None	None	None	None	N
D/S	0.1954	likely_benign	0.1841	benign	-1.181	Destabilizing	0.134	N	0.463	neutral	None	None	None	None	N
D/T	0.2595	likely_benign	0.2299	benign	-0.85	Destabilizing	0.519	D	0.539	neutral	None	None	None	None	N
D/V	0.1672	likely_benign	0.1526	benign	0.323	Stabilizing	0.449	N	0.675	prob.neutral	N	0.447955216	None	None	N
D/W	0.8809	likely_pathogenic	0.8692	pathogenic	0.488	Stabilizing	0.962	D	0.648	neutral	None	None	None	None	N
D/Y	0.268	likely_benign	0.246	benign	0.53	Stabilizing	0.834	D	0.718	prob.delet.	N	0.51708444	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.