TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9029	27310;27311;27312	chr2:178712940;178712939;178712938	chr2:179577667;179577666;179577665
N2AB	8712	26359;26360;26361	chr2:178712940;178712939;178712938	chr2:179577667;179577666;179577665
N2A	7785	23578;23579;23580	chr2:178712940;178712939;178712938	chr2:179577667;179577666;179577665
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-76
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.7858
• 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	rs1336740450	-0.051	0.669	N	0.343	0.337	0.265010934533	gnomAD-2.1.1	6.37E-05	None	None	None	None	N	None	2.29621E-04	0	None	0	0	None	0	None	0	0	0
D/G	rs1336740450	-0.051	0.669	N	0.343	0.337	0.265010934533	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	2.07211E-04	0
D/G	rs1336740450	-0.051	0.669	N	0.343	0.337	0.265010934533	gnomAD-4.0.0	4.05966E-06	None	None	None	None	N	None	5.24054E-05	0	None	0	0	None	0	0	0	4.69792E-05	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	0.1301	likely_benign	0.1505	benign	-0.372	Destabilizing	0.801	D	0.362	neutral	N	0.445341772	None	None	N
D/C	0.6074	likely_pathogenic	0.6678	pathogenic	-0.228	Destabilizing	0.998	D	0.439	neutral	None	None	None	None	N
D/E	0.1147	likely_benign	0.1182	benign	-0.282	Destabilizing	0.005	N	0.153	neutral	N	0.35418105	None	None	N
D/F	0.4745	ambiguous	0.5406	ambiguous	0.088	Stabilizing	0.991	D	0.399	neutral	None	None	None	None	N
D/G	0.1823	likely_benign	0.2256	benign	-0.639	Destabilizing	0.669	D	0.343	neutral	N	0.503563356	None	None	N
D/H	0.2168	likely_benign	0.2507	benign	0.257	Stabilizing	0.966	D	0.359	neutral	N	0.485150954	None	None	N
D/I	0.2501	likely_benign	0.2817	benign	0.309	Stabilizing	0.974	D	0.404	neutral	None	None	None	None	N
D/K	0.2998	likely_benign	0.3632	ambiguous	0.143	Stabilizing	0.728	D	0.343	neutral	None	None	None	None	N
D/L	0.2822	likely_benign	0.3298	benign	0.309	Stabilizing	0.842	D	0.409	neutral	None	None	None	None	N
D/M	0.4488	ambiguous	0.4934	ambiguous	0.363	Stabilizing	0.993	D	0.381	neutral	None	None	None	None	N
D/N	0.0932	likely_benign	0.0964	benign	-0.415	Destabilizing	0.005	N	0.153	neutral	N	0.450787664	None	None	N
D/P	0.5883	likely_pathogenic	0.7001	pathogenic	0.106	Stabilizing	0.974	D	0.367	neutral	None	None	None	None	N
D/Q	0.2486	likely_benign	0.2861	benign	-0.312	Destabilizing	0.067	N	0.185	neutral	None	None	None	None	N
D/R	0.3282	likely_benign	0.3985	ambiguous	0.452	Stabilizing	0.728	D	0.377	neutral	None	None	None	None	N
D/S	0.1218	likely_benign	0.1308	benign	-0.542	Destabilizing	0.525	D	0.307	neutral	None	None	None	None	N
D/T	0.1864	likely_benign	0.2007	benign	-0.317	Destabilizing	0.842	D	0.335	neutral	None	None	None	None	N
D/V	0.135	likely_benign	0.1507	benign	0.106	Stabilizing	0.966	D	0.395	neutral	N	0.405340589	None	None	N
D/W	0.7891	likely_pathogenic	0.8526	pathogenic	0.329	Stabilizing	0.998	D	0.539	neutral	None	None	None	None	N
D/Y	0.1707	likely_benign	0.2094	benign	0.352	Stabilizing	0.989	D	0.397	neutral	N	0.474549958	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.