TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32822	98689;98690;98691	chr2:178539601;178539600;178539599	chr2:179404328;179404327;179404326
N2AB	31181	93766;93767;93768	chr2:178539601;178539600;178539599	chr2:179404328;179404327;179404326
N2A	30254	90985;90986;90987	chr2:178539601;178539600;178539599	chr2:179404328;179404327;179404326
N2B	23757	71494;71495;71496	chr2:178539601;178539600;178539599	chr2:179404328;179404327;179404326
Novex-1	23882	71869;71870;71871	chr2:178539601;178539600;178539599	chr2:179404328;179404327;179404326
Novex-2	23949	72070;72071;72072	chr2:178539601;178539600;178539599	chr2:179404328;179404327;179404326
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: Fn3-127
• Domain position: 28
• Structural Position: 29
• Q(SASA): 0.6664
• 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	rs191054704	0.131	1.0	N	0.689	0.463	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92604E-04	None	0	0	0	0	0
D/A	rs191054704	0.131	1.0	N	0.689	0.463	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
D/A	rs191054704	0.131	1.0	N	0.689	0.463	None	gnomAD-4.0.0	6.56711E-06	None	None	None	None	N	None	0	0	None	0	1.9305E-04	None	0	0	0	0	0
D/G	rs191054704	-0.106	1.0	N	0.646	0.513	0.32580497728	gnomAD-2.1.1	5.72E-05	None	None	None	None	N	None	0	2.83E-05	None	0	7.68285E-04	None	0	None	0	0	0
D/G	rs191054704	-0.106	1.0	N	0.646	0.513	0.32580497728	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	5.77812E-04	None	0	0	0	0	0
D/G	rs191054704	-0.106	1.0	N	0.646	0.513	0.32580497728	gnomAD-4.0.0	2.60262E-05	None	None	None	None	N	None	0	1.66667E-05	None	0	6.45995E-04	None	0	0	0	0	1.92135E-04
D/N	rs921446344	0.655	1.0	N	0.626	0.364	0.288352970974	gnomAD-2.1.1	7.14E-06	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	0	None	0	7.82E-06	0
D/N	rs921446344	0.655	1.0	N	0.626	0.364	0.288352970974	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
D/N	rs921446344	0.655	1.0	N	0.626	0.364	0.288352970974	gnomAD-4.0.0	5.57708E-06	None	None	None	None	N	None	1.33515E-05	0	None	0	0	None	0	0	6.78075E-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	0.5267	ambiguous	0.486	ambiguous	-0.215	Destabilizing	1.0	D	0.689	prob.neutral	N	0.474415026	None	None	N
D/C	0.8651	likely_pathogenic	0.8243	pathogenic	0.263	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	N
D/E	0.3426	ambiguous	0.2998	benign	-0.376	Destabilizing	1.0	D	0.385	neutral	N	0.503556917	None	None	N
D/F	0.8529	likely_pathogenic	0.8134	pathogenic	-0.427	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
D/G	0.5965	likely_pathogenic	0.5665	pathogenic	-0.395	Destabilizing	1.0	D	0.646	neutral	N	0.485379711	None	None	N
D/H	0.6942	likely_pathogenic	0.6306	pathogenic	-0.437	Destabilizing	1.0	D	0.6	neutral	N	0.468667808	None	None	N
D/I	0.6884	likely_pathogenic	0.6509	pathogenic	0.202	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
D/K	0.7832	likely_pathogenic	0.7455	pathogenic	0.343	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
D/L	0.7131	likely_pathogenic	0.68	pathogenic	0.202	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
D/M	0.8537	likely_pathogenic	0.832	pathogenic	0.487	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
D/N	0.1801	likely_benign	0.1665	benign	0.191	Stabilizing	1.0	D	0.626	neutral	N	0.488472821	None	None	N
D/P	0.9796	likely_pathogenic	0.976	pathogenic	0.085	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
D/Q	0.6942	likely_pathogenic	0.6502	pathogenic	0.195	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
D/R	0.8007	likely_pathogenic	0.7667	pathogenic	0.363	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
D/S	0.3231	likely_benign	0.3003	benign	0.084	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	N
D/T	0.5177	ambiguous	0.5268	ambiguous	0.215	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
D/V	0.4765	ambiguous	0.4424	ambiguous	0.085	Stabilizing	1.0	D	0.717	prob.delet.	N	0.478440724	None	None	N
D/W	0.9703	likely_pathogenic	0.9614	pathogenic	-0.389	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
D/Y	0.5645	likely_pathogenic	0.4816	ambiguous	-0.212	Destabilizing	1.0	D	0.633	neutral	N	0.451373247	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.