TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30336	91231;91232;91233	chr2:178551894;178551893;178551892	chr2:179416621;179416620;179416619
N2AB	28695	86308;86309;86310	chr2:178551894;178551893;178551892	chr2:179416621;179416620;179416619
N2A	27768	83527;83528;83529	chr2:178551894;178551893;178551892	chr2:179416621;179416620;179416619
N2B	21271	64036;64037;64038	chr2:178551894;178551893;178551892	chr2:179416621;179416620;179416619
Novex-1	21396	64411;64412;64413	chr2:178551894;178551893;178551892	chr2:179416621;179416620;179416619
Novex-2	21463	64612;64613;64614	chr2:178551894;178551893;178551892	chr2:179416621;179416620;179416619
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-109
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.222
• Predicted PPI site: I

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
V/A	None	None	0.645	D	0.423	0.324	0.585564602418	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.407	ambiguous	0.4555	ambiguous	-1.152	Destabilizing	0.645	D	0.423	neutral	D	0.524351555	None	None	I
V/C	0.8413	likely_pathogenic	0.8382	pathogenic	-1.301	Destabilizing	0.995	D	0.62	neutral	None	None	None	None	I
V/D	0.9034	likely_pathogenic	0.9052	pathogenic	-2.019	Highly Destabilizing	0.945	D	0.75	deleterious	None	None	None	None	I
V/E	0.7973	likely_pathogenic	0.7786	pathogenic	-2.062	Highly Destabilizing	0.928	D	0.683	prob.neutral	N	0.510885885	None	None	I
V/F	0.5251	ambiguous	0.5206	ambiguous	-1.371	Destabilizing	0.894	D	0.64	neutral	None	None	None	None	I
V/G	0.6441	likely_pathogenic	0.6569	pathogenic	-1.369	Destabilizing	0.928	D	0.743	deleterious	N	0.507633882	None	None	I
V/H	0.9112	likely_pathogenic	0.8994	pathogenic	-0.984	Destabilizing	0.995	D	0.727	prob.delet.	None	None	None	None	I
V/I	0.0755	likely_benign	0.0775	benign	-0.667	Destabilizing	0.003	N	0.176	neutral	None	None	None	None	I
V/K	0.7863	likely_pathogenic	0.7521	pathogenic	-0.942	Destabilizing	0.945	D	0.688	prob.neutral	None	None	None	None	I
V/L	0.4732	ambiguous	0.4827	ambiguous	-0.667	Destabilizing	0.114	N	0.299	neutral	N	0.474068264	None	None	I
V/M	0.2969	likely_benign	0.3021	benign	-0.574	Destabilizing	0.864	D	0.574	neutral	N	0.482439283	None	None	I
V/N	0.6814	likely_pathogenic	0.7059	pathogenic	-0.941	Destabilizing	0.981	D	0.741	deleterious	None	None	None	None	I
V/P	0.8569	likely_pathogenic	0.8817	pathogenic	-0.798	Destabilizing	0.981	D	0.697	prob.neutral	None	None	None	None	I
V/Q	0.7367	likely_pathogenic	0.7004	pathogenic	-1.253	Destabilizing	0.981	D	0.685	prob.neutral	None	None	None	None	I
V/R	0.7397	likely_pathogenic	0.6899	pathogenic	-0.437	Destabilizing	0.945	D	0.738	prob.delet.	None	None	None	None	I
V/S	0.5512	ambiguous	0.5941	pathogenic	-1.288	Destabilizing	0.945	D	0.681	prob.neutral	None	None	None	None	I
V/T	0.3653	ambiguous	0.3991	ambiguous	-1.238	Destabilizing	0.707	D	0.513	neutral	None	None	None	None	I
V/W	0.9764	likely_pathogenic	0.9744	pathogenic	-1.537	Destabilizing	0.995	D	0.706	prob.neutral	None	None	None	None	I
V/Y	0.8843	likely_pathogenic	0.874	pathogenic	-1.15	Destabilizing	0.945	D	0.649	neutral	None	None	None	None	I

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.