TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4669	14230;14231;14232	chr2:178739228;178739227;178739226	chr2:179603955;179603954;179603953
N2AB	4352	13279;13280;13281	chr2:178739228;178739227;178739226	chr2:179603955;179603954;179603953
N2A	None	None	chr2:None	chr2:None
N2B	4306	13141;13142;13143	chr2:178739228;178739227;178739226	chr2:179603955;179603954;179603953
Novex-1	4431	13516;13517;13518	chr2:178739228;178739227;178739226	chr2:179603955;179603954;179603953
Novex-2	4498	13717;13718;13719	chr2:178739228;178739227;178739226	chr2:179603955;179603954;179603953
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: Ig-29
• Domain position: 64
• Structural Position: 148
• Q(SASA): 0.569
• 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/G	None	None	0.698	D	0.517	0.279	0.307966526162	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs368543748	0.451	0.075	N	0.297	0.201	0.261217442401	gnomAD-2.1.1	7.44E-05	None	None	None	None	N	None	0	0	None	0	7.93651E-04	None	0	None	0	2.87E-05	0
E/K	rs368543748	0.451	0.075	N	0.297	0.201	0.261217442401	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	2.41E-05	0	0	0	5.78481E-04	None	0	0	2.94E-05	0	0
E/K	rs368543748	0.451	0.075	N	0.297	0.201	0.261217442401	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
E/K	rs368543748	0.451	0.075	N	0.297	0.201	0.261217442401	gnomAD-4.0.0	3.67032E-05	None	None	None	None	N	None	1.34405E-05	0	None	0	4.7357E-04	None	0	0	2.75838E-05	1.17523E-05	4.91819E-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	0.1117	likely_benign	0.1101	benign	-0.03	Destabilizing	0.698	D	0.525	neutral	N	0.483739863	None	None	N
E/C	0.7154	likely_pathogenic	0.7155	pathogenic	0.149	Stabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
E/D	0.127	likely_benign	0.1281	benign	-0.137	Destabilizing	0.014	N	0.226	neutral	N	0.470275751	None	None	N
E/F	0.5948	likely_pathogenic	0.6021	pathogenic	-0.187	Destabilizing	0.993	D	0.632	neutral	None	None	None	None	N
E/G	0.1147	likely_benign	0.1182	benign	-0.141	Destabilizing	0.698	D	0.517	neutral	D	0.543899119	None	None	N
E/H	0.3331	likely_benign	0.3242	benign	0.237	Stabilizing	0.978	D	0.478	neutral	None	None	None	None	N
E/I	0.2596	likely_benign	0.2538	benign	0.201	Stabilizing	0.978	D	0.627	neutral	None	None	None	None	N
E/K	0.0805	likely_benign	0.0777	benign	0.573	Stabilizing	0.075	N	0.297	neutral	N	0.503101119	None	None	N
E/L	0.2914	likely_benign	0.2847	benign	0.201	Stabilizing	0.956	D	0.567	neutral	None	None	None	None	N
E/M	0.317	likely_benign	0.3177	benign	0.182	Stabilizing	0.998	D	0.604	neutral	None	None	None	None	N
E/N	0.1957	likely_benign	0.1969	benign	0.479	Stabilizing	0.043	N	0.285	neutral	None	None	None	None	N
E/P	0.5067	ambiguous	0.5393	ambiguous	0.142	Stabilizing	0.978	D	0.523	neutral	None	None	None	None	N
E/Q	0.1211	likely_benign	0.115	benign	0.466	Stabilizing	0.922	D	0.475	neutral	N	0.496354177	None	None	N
E/R	0.1403	likely_benign	0.1384	benign	0.672	Stabilizing	0.915	D	0.475	neutral	None	None	None	None	N
E/S	0.1501	likely_benign	0.1513	benign	0.305	Stabilizing	0.754	D	0.504	neutral	None	None	None	None	N
E/T	0.152	likely_benign	0.15	benign	0.397	Stabilizing	0.86	D	0.498	neutral	None	None	None	None	N
E/V	0.1527	likely_benign	0.1511	benign	0.142	Stabilizing	0.942	D	0.537	neutral	D	0.619441517	None	None	N
E/W	0.7297	likely_pathogenic	0.7381	pathogenic	-0.168	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
E/Y	0.4868	ambiguous	0.4904	ambiguous	0.037	Stabilizing	0.993	D	0.597	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.