TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28220	84883;84884;84885	chr2:178561474;178561473;178561472	chr2:179426201;179426200;179426199
N2AB	26579	79960;79961;79962	chr2:178561474;178561473;178561472	chr2:179426201;179426200;179426199
N2A	25652	77179;77180;77181	chr2:178561474;178561473;178561472	chr2:179426201;179426200;179426199
N2B	19155	57688;57689;57690	chr2:178561474;178561473;178561472	chr2:179426201;179426200;179426199
Novex-1	19280	58063;58064;58065	chr2:178561474;178561473;178561472	chr2:179426201;179426200;179426199
Novex-2	19347	58264;58265;58266	chr2:178561474;178561473;178561472	chr2:179426201;179426200;179426199
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: Fn3-93
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.5469
• 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	0.815	N	0.398	0.285	0.302793454619	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85829E-06	0	0
D/H	rs538385596	0.184	0.939	N	0.467	0.318	0.316198179892	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
D/H	rs538385596	0.184	0.939	N	0.467	0.318	0.316198179892	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/H	rs538385596	0.184	0.939	N	0.467	0.318	0.316198179892	gnomAD-4.0.0	1.85912E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54285E-06	0	0
D/N	rs538385596	-0.203	0.684	N	0.426	0.194	0.268660756437	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
D/N	rs538385596	-0.203	0.684	N	0.426	0.194	0.268660756437	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/N	rs538385596	-0.203	0.684	N	0.426	0.194	0.268660756437	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
D/N	rs538385596	-0.203	0.684	N	0.426	0.194	0.268660756437	gnomAD-4.0.0	6.84229E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99478E-07	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	0.1582	likely_benign	0.1527	benign	-0.166	Destabilizing	0.684	D	0.385	neutral	N	0.4528326	None	None	N
D/C	0.579	likely_pathogenic	0.5634	ambiguous	-0.088	Destabilizing	0.996	D	0.569	neutral	None	None	None	None	N
D/E	0.0966	likely_benign	0.0935	benign	-0.284	Destabilizing	0.003	N	0.116	neutral	N	0.351436241	None	None	N
D/F	0.5996	likely_pathogenic	0.5767	pathogenic	0.299	Stabilizing	0.91	D	0.533	neutral	None	None	None	None	N
D/G	0.2218	likely_benign	0.2104	benign	-0.424	Destabilizing	0.815	D	0.398	neutral	N	0.516094644	None	None	N
D/H	0.2535	likely_benign	0.2459	benign	0.607	Stabilizing	0.939	D	0.467	neutral	N	0.45144852	None	None	N
D/I	0.2764	likely_benign	0.2575	benign	0.485	Stabilizing	0.835	D	0.471	neutral	None	None	None	None	N
D/K	0.3289	likely_benign	0.3064	benign	0.538	Stabilizing	0.59	D	0.37	neutral	None	None	None	None	N
D/L	0.3072	likely_benign	0.2964	benign	0.485	Stabilizing	0.009	N	0.339	neutral	None	None	None	None	N
D/M	0.4789	ambiguous	0.4551	ambiguous	0.466	Stabilizing	0.974	D	0.531	neutral	None	None	None	None	N
D/N	0.1289	likely_benign	0.1225	benign	-0.185	Destabilizing	0.684	D	0.426	neutral	N	0.43594035	None	None	N
D/P	0.7351	likely_pathogenic	0.736	pathogenic	0.291	Stabilizing	0.953	D	0.447	neutral	None	None	None	None	N
D/Q	0.24	likely_benign	0.2296	benign	-0.064	Destabilizing	0.835	D	0.378	neutral	None	None	None	None	N
D/R	0.3615	ambiguous	0.3345	benign	0.821	Stabilizing	0.91	D	0.466	neutral	None	None	None	None	N
D/S	0.1292	likely_benign	0.125	benign	-0.255	Destabilizing	0.742	D	0.344	neutral	None	None	None	None	N
D/T	0.1912	likely_benign	0.1885	benign	-0.017	Destabilizing	0.742	D	0.422	neutral	None	None	None	None	N
D/V	0.1536	likely_benign	0.1461	benign	0.291	Stabilizing	0.521	D	0.435	neutral	N	0.427416867	None	None	N
D/W	0.8605	likely_pathogenic	0.8554	pathogenic	0.54	Stabilizing	0.996	D	0.645	neutral	None	None	None	None	N
D/Y	0.2297	likely_benign	0.2201	benign	0.596	Stabilizing	0.939	D	0.535	neutral	N	0.478653764	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.