TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28170	84733;84734;84735	chr2:178561624;178561623;178561622	chr2:179426351;179426350;179426349
N2AB	26529	79810;79811;79812	chr2:178561624;178561623;178561622	chr2:179426351;179426350;179426349
N2A	25602	77029;77030;77031	chr2:178561624;178561623;178561622	chr2:179426351;179426350;179426349
N2B	19105	57538;57539;57540	chr2:178561624;178561623;178561622	chr2:179426351;179426350;179426349
Novex-1	19230	57913;57914;57915	chr2:178561624;178561623;178561622	chr2:179426351;179426350;179426349
Novex-2	19297	58114;58115;58116	chr2:178561624;178561623;178561622	chr2:179426351;179426350;179426349
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-93
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1644
• 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
T/A	rs1703689855	None	0.08	N	0.316	0.082	0.149567049428	gnomAD-4.0.0	1.59467E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86344E-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
T/A	0.072	likely_benign	0.0693	benign	-0.748	Destabilizing	0.08	N	0.316	neutral	N	0.470709071	None	None	N
T/C	0.2966	likely_benign	0.2722	benign	-0.63	Destabilizing	0.991	D	0.604	neutral	None	None	None	None	N
T/D	0.3741	ambiguous	0.3458	ambiguous	-1.196	Destabilizing	0.209	N	0.463	neutral	None	None	None	None	N
T/E	0.3408	ambiguous	0.3257	benign	-1.172	Destabilizing	0.002	N	0.327	neutral	None	None	None	None	N
T/F	0.1868	likely_benign	0.159	benign	-0.859	Destabilizing	0.002	N	0.403	neutral	None	None	None	None	N
T/G	0.1752	likely_benign	0.1586	benign	-1.019	Destabilizing	0.001	N	0.371	neutral	None	None	None	None	N
T/H	0.2072	likely_benign	0.1852	benign	-1.388	Destabilizing	0.901	D	0.627	neutral	None	None	None	None	N
T/I	0.2322	likely_benign	0.2212	benign	-0.107	Destabilizing	0.326	N	0.531	neutral	N	0.520137814	None	None	N
T/K	0.3353	likely_benign	0.3228	benign	-0.839	Destabilizing	0.209	N	0.483	neutral	None	None	None	None	N
T/L	0.1161	likely_benign	0.1082	benign	-0.107	Destabilizing	0.209	N	0.443	neutral	None	None	None	None	N
T/M	0.0909	likely_benign	0.0885	benign	0.289	Stabilizing	0.901	D	0.62	neutral	None	None	None	None	N
T/N	0.1022	likely_benign	0.0983	benign	-1.009	Destabilizing	0.491	N	0.401	neutral	N	0.492873855	None	None	N
T/P	0.7489	likely_pathogenic	0.7875	pathogenic	-0.289	Destabilizing	0.662	D	0.59	neutral	N	0.482893355	None	None	N
T/Q	0.2233	likely_benign	0.2174	benign	-1.221	Destabilizing	0.39	N	0.598	neutral	None	None	None	None	N
T/R	0.2508	likely_benign	0.2377	benign	-0.58	Destabilizing	0.561	D	0.591	neutral	None	None	None	None	N
T/S	0.0713	likely_benign	0.067	benign	-1.141	Destabilizing	0.005	N	0.138	neutral	N	0.353702969	None	None	N
T/V	0.1523	likely_benign	0.1466	benign	-0.289	Destabilizing	0.345	N	0.356	neutral	None	None	None	None	N
T/W	0.5459	ambiguous	0.4977	ambiguous	-0.866	Destabilizing	0.991	D	0.603	neutral	None	None	None	None	N
T/Y	0.2066	likely_benign	0.1751	benign	-0.571	Destabilizing	0.39	N	0.609	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.