TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21386	64381;64382;64383	chr2:178586745;178586744;178586743	chr2:179451472;179451471;179451470
N2AB	19745	59458;59459;59460	chr2:178586745;178586744;178586743	chr2:179451472;179451471;179451470
N2A	18818	56677;56678;56679	chr2:178586745;178586744;178586743	chr2:179451472;179451471;179451470
N2B	12321	37186;37187;37188	chr2:178586745;178586744;178586743	chr2:179451472;179451471;179451470
Novex-1	12446	37561;37562;37563	chr2:178586745;178586744;178586743	chr2:179451472;179451471;179451470
Novex-2	12513	37762;37763;37764	chr2:178586745;178586744;178586743	chr2:179451472;179451471;179451470
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-43
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1464
• 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
A/V	None	None	0.103	N	0.436	0.136	0.361160317528	gnomAD-4.0.0	1.36897E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15966E-05	1.65755E-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
A/C	0.3991	ambiguous	0.3493	ambiguous	-0.9	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
A/D	0.6368	likely_pathogenic	0.5124	ambiguous	-1.758	Destabilizing	0.984	D	0.699	prob.neutral	N	0.505859008	None	None	N
A/E	0.4725	ambiguous	0.3464	ambiguous	-1.614	Destabilizing	0.988	D	0.699	prob.neutral	None	None	None	None	N
A/F	0.3779	ambiguous	0.3203	benign	-0.631	Destabilizing	0.988	D	0.723	prob.delet.	None	None	None	None	N
A/G	0.1352	likely_benign	0.1468	benign	-1.225	Destabilizing	0.004	N	0.234	neutral	N	0.426936865	None	None	N
A/H	0.4985	ambiguous	0.4065	ambiguous	-1.761	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
A/I	0.2851	likely_benign	0.2197	benign	0.329	Stabilizing	0.851	D	0.689	prob.neutral	None	None	None	None	N
A/K	0.5732	likely_pathogenic	0.4324	ambiguous	-1.063	Destabilizing	0.988	D	0.695	prob.neutral	None	None	None	None	N
A/L	0.1952	likely_benign	0.1515	benign	0.329	Stabilizing	0.851	D	0.639	neutral	None	None	None	None	N
A/M	0.2485	likely_benign	0.2028	benign	0.114	Stabilizing	0.997	D	0.685	prob.neutral	None	None	None	None	N
A/N	0.3611	ambiguous	0.292	benign	-1.2	Destabilizing	0.976	D	0.699	prob.neutral	None	None	None	None	N
A/P	0.9585	likely_pathogenic	0.947	pathogenic	0.002	Stabilizing	0.995	D	0.697	prob.neutral	N	0.489246003	None	None	N
A/Q	0.353	ambiguous	0.2932	benign	-1.071	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	N
A/R	0.4751	ambiguous	0.3666	ambiguous	-1.118	Destabilizing	0.988	D	0.71	prob.delet.	None	None	None	None	N
A/S	0.0982	likely_benign	0.0916	benign	-1.606	Destabilizing	0.896	D	0.547	neutral	N	0.398224537	None	None	N
A/T	0.1012	likely_benign	0.0831	benign	-1.337	Destabilizing	0.896	D	0.627	neutral	N	0.415967723	None	None	N
A/V	0.1643	likely_benign	0.1281	benign	0.002	Stabilizing	0.103	N	0.436	neutral	N	0.476749609	None	None	N
A/W	0.7903	likely_pathogenic	0.7219	pathogenic	-1.37	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
A/Y	0.5017	ambiguous	0.4158	ambiguous	-0.762	Destabilizing	0.996	D	0.735	prob.delet.	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.