TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35030	105313;105314;105315	chr2:178531527;178531526;178531525	chr2:179396254;179396253;179396252
N2AB	33389	100390;100391;100392	chr2:178531527;178531526;178531525	chr2:179396254;179396253;179396252
N2A	32462	97609;97610;97611	chr2:178531527;178531526;178531525	chr2:179396254;179396253;179396252
N2B	25965	78118;78119;78120	chr2:178531527;178531526;178531525	chr2:179396254;179396253;179396252
Novex-1	26090	78493;78494;78495	chr2:178531527;178531526;178531525	chr2:179396254;179396253;179396252
Novex-2	26157	78694;78695;78696	chr2:178531527;178531526;178531525	chr2:179396254;179396253;179396252
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: Ig-163
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3682
• 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	rs72629789	-0.179	0.893	N	0.351	0.173	0.101711395817	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
D/E	rs72629789	-0.179	0.893	N	0.351	0.173	0.101711395817	gnomAD-4.0.0	6.84177E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	0
D/G	rs773386284	-0.747	0.998	N	0.749	0.517	0.388334884743	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
D/G	rs773386284	-0.747	0.998	N	0.749	0.517	0.388334884743	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/G	rs773386284	-0.747	0.998	N	0.749	0.517	0.388334884743	gnomAD-4.0.0	4.33747E-06	None	None	None	None	N	None	0	0	None	0	2.22717E-05	None	0	0	5.0853E-06	0	0
D/H	None	None	1.0	N	0.731	0.433	0.392395365052	gnomAD-4.0.0	6.84167E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99402E-07	0	0
D/N	rs1689108955	None	0.999	N	0.715	0.333	0.329540904979	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/N	rs1689108955	None	0.999	N	0.715	0.333	0.329540904979	gnomAD-4.0.0	4.95718E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.78037E-06	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	0.5378	ambiguous	0.6117	pathogenic	-0.489	Destabilizing	0.999	D	0.739	prob.delet.	N	0.481801218	None	None	N
D/C	0.9401	likely_pathogenic	0.962	pathogenic	0.074	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
D/E	0.3937	ambiguous	0.4745	ambiguous	-0.57	Destabilizing	0.893	D	0.351	neutral	N	0.434682061	None	None	N
D/F	0.8768	likely_pathogenic	0.9182	pathogenic	-0.62	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
D/G	0.719	likely_pathogenic	0.7805	pathogenic	-0.728	Destabilizing	0.998	D	0.749	deleterious	N	0.512990916	None	None	N
D/H	0.666	likely_pathogenic	0.7509	pathogenic	-0.873	Destabilizing	1.0	D	0.731	prob.delet.	N	0.493962438	None	None	N
D/I	0.7705	likely_pathogenic	0.8339	pathogenic	0.106	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
D/K	0.87	likely_pathogenic	0.9038	pathogenic	0.146	Stabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
D/L	0.7309	likely_pathogenic	0.7977	pathogenic	0.106	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
D/M	0.8951	likely_pathogenic	0.9286	pathogenic	0.534	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
D/N	0.3207	likely_benign	0.3957	ambiguous	-0.126	Destabilizing	0.999	D	0.715	prob.delet.	N	0.457713637	None	None	N
D/P	0.9917	likely_pathogenic	0.9931	pathogenic	-0.069	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
D/Q	0.749	likely_pathogenic	0.8036	pathogenic	-0.106	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
D/R	0.8406	likely_pathogenic	0.8845	pathogenic	0.091	Stabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
D/S	0.4043	ambiguous	0.4819	ambiguous	-0.286	Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	N
D/T	0.6583	likely_pathogenic	0.7264	pathogenic	-0.094	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
D/V	0.5639	ambiguous	0.6455	pathogenic	-0.069	Destabilizing	0.999	D	0.783	deleterious	N	0.426988085	None	None	N
D/W	0.974	likely_pathogenic	0.9826	pathogenic	-0.527	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
D/Y	0.6011	likely_pathogenic	0.7002	pathogenic	-0.381	Destabilizing	1.0	D	0.785	deleterious	N	0.494482513	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.