TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18103	54532;54533;54534	chr2:178604782;178604781;178604780	chr2:179469509;179469508;179469507
N2AB	16462	49609;49610;49611	chr2:178604782;178604781;178604780	chr2:179469509;179469508;179469507
N2A	15535	46828;46829;46830	chr2:178604782;178604781;178604780	chr2:179469509;179469508;179469507
N2B	9038	27337;27338;27339	chr2:178604782;178604781;178604780	chr2:179469509;179469508;179469507
Novex-1	9163	27712;27713;27714	chr2:178604782;178604781;178604780	chr2:179469509;179469508;179469507
Novex-2	9230	27913;27914;27915	chr2:178604782;178604781;178604780	chr2:179469509;179469508;179469507
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: Fn3-19
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0959
• 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/G	None	None	0.939	N	0.712	0.461	0.242244723065	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
D/N	rs1193175329	None	0.939	N	0.702	0.265	0.215109475489	gnomAD-4.0.0	1.36959E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80013E-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	0.5715	likely_pathogenic	0.5603	ambiguous	-1.959	Destabilizing	0.939	D	0.71	prob.delet.	N	0.466108541	None	None	N
D/C	0.8537	likely_pathogenic	0.8436	pathogenic	-0.908	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
D/E	0.267	likely_benign	0.2844	benign	-1.083	Destabilizing	0.02	N	0.373	neutral	N	0.302047571	None	None	N
D/F	0.8163	likely_pathogenic	0.8372	pathogenic	-1.796	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
D/G	0.6661	likely_pathogenic	0.7001	pathogenic	-2.304	Highly Destabilizing	0.939	D	0.712	prob.delet.	N	0.491833705	None	None	N
D/H	0.6686	likely_pathogenic	0.6766	pathogenic	-1.488	Destabilizing	0.998	D	0.75	deleterious	N	0.49131363	None	None	N
D/I	0.8302	likely_pathogenic	0.8316	pathogenic	-0.974	Destabilizing	0.993	D	0.819	deleterious	None	None	None	None	N
D/K	0.9068	likely_pathogenic	0.9173	pathogenic	-1.668	Destabilizing	0.91	D	0.697	prob.neutral	None	None	None	None	N
D/L	0.7723	likely_pathogenic	0.7675	pathogenic	-0.974	Destabilizing	0.986	D	0.781	deleterious	None	None	None	None	N
D/M	0.8872	likely_pathogenic	0.8938	pathogenic	-0.232	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
D/N	0.3727	ambiguous	0.39	ambiguous	-1.74	Destabilizing	0.939	D	0.702	prob.neutral	N	0.480885993	None	None	N
D/P	0.9981	likely_pathogenic	0.9981	pathogenic	-1.289	Destabilizing	0.993	D	0.732	prob.delet.	None	None	None	None	N
D/Q	0.666	likely_pathogenic	0.6801	pathogenic	-1.461	Destabilizing	0.973	D	0.734	prob.delet.	None	None	None	None	N
D/R	0.9061	likely_pathogenic	0.9176	pathogenic	-1.502	Destabilizing	0.986	D	0.731	prob.delet.	None	None	None	None	N
D/S	0.3799	ambiguous	0.3863	ambiguous	-2.413	Highly Destabilizing	0.953	D	0.671	neutral	None	None	None	None	N
D/T	0.6763	likely_pathogenic	0.6979	pathogenic	-2.071	Highly Destabilizing	0.986	D	0.731	prob.delet.	None	None	None	None	N
D/V	0.6649	likely_pathogenic	0.6635	pathogenic	-1.289	Destabilizing	0.991	D	0.777	deleterious	N	0.491140272	None	None	N
D/W	0.9607	likely_pathogenic	0.9649	pathogenic	-1.881	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
D/Y	0.5799	likely_pathogenic	0.6056	pathogenic	-1.631	Destabilizing	0.997	D	0.809	deleterious	N	0.432670758	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.