TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24777	74554;74555;74556	chr2:178571803;178571802;178571801	chr2:179436530;179436529;179436528
N2AB	23136	69631;69632;69633	chr2:178571803;178571802;178571801	chr2:179436530;179436529;179436528
N2A	22209	66850;66851;66852	chr2:178571803;178571802;178571801	chr2:179436530;179436529;179436528
N2B	15712	47359;47360;47361	chr2:178571803;178571802;178571801	chr2:179436530;179436529;179436528
Novex-1	15837	47734;47735;47736	chr2:178571803;178571802;178571801	chr2:179436530;179436529;179436528
Novex-2	15904	47935;47936;47937	chr2:178571803;178571802;178571801	chr2:179436530;179436529;179436528
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: Ig-133
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.7718
• 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	0.001	N	0.249	0.167	0.168933306366	gnomAD-4.0.0	1.59276E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86123E-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	0.2634	likely_benign	0.2329	benign	-0.156	Destabilizing	None	N	0.146	neutral	N	0.503020986	None	None	N
D/C	0.813	likely_pathogenic	0.7695	pathogenic	0.274	Stabilizing	0.316	N	0.346	neutral	None	None	None	None	N
D/E	0.0723	likely_benign	0.0687	benign	-0.375	Destabilizing	None	N	0.079	neutral	N	0.419730386	None	None	N
D/F	0.8094	likely_pathogenic	0.7762	pathogenic	-0.426	Destabilizing	0.051	N	0.405	neutral	None	None	None	None	N
D/G	0.2199	likely_benign	0.2016	benign	-0.358	Destabilizing	0.001	N	0.249	neutral	N	0.479066691	None	None	N
D/H	0.5239	ambiguous	0.4815	ambiguous	-0.605	Destabilizing	0.013	N	0.321	neutral	N	0.497884525	None	None	N
D/I	0.6459	likely_pathogenic	0.6032	pathogenic	0.325	Stabilizing	0.018	N	0.328	neutral	None	None	None	None	N
D/K	0.5147	ambiguous	0.4779	ambiguous	0.214	Stabilizing	None	N	0.137	neutral	None	None	None	None	N
D/L	0.5621	ambiguous	0.5246	ambiguous	0.325	Stabilizing	0.002	N	0.267	neutral	None	None	None	None	N
D/M	0.6984	likely_pathogenic	0.6557	pathogenic	0.671	Stabilizing	0.116	N	0.443	neutral	None	None	None	None	N
D/N	0.1581	likely_benign	0.1429	benign	0.106	Stabilizing	0.001	N	0.176	neutral	N	0.435465055	None	None	N
D/P	0.9442	likely_pathogenic	0.9316	pathogenic	0.188	Stabilizing	0.003	N	0.249	neutral	None	None	None	None	N
D/Q	0.3765	ambiguous	0.3486	ambiguous	0.121	Stabilizing	None	N	0.163	neutral	None	None	None	None	N
D/R	0.6479	likely_pathogenic	0.607	pathogenic	0.189	Stabilizing	0.001	N	0.219	neutral	None	None	None	None	N
D/S	0.2214	likely_benign	0.1994	benign	-0.035	Destabilizing	None	N	0.156	neutral	None	None	None	None	N
D/T	0.3788	ambiguous	0.3517	ambiguous	0.11	Stabilizing	0.002	N	0.269	neutral	None	None	None	None	N
D/V	0.391	ambiguous	0.3568	ambiguous	0.188	Stabilizing	0.001	N	0.273	neutral	N	0.456834657	None	None	N
D/W	0.9463	likely_pathogenic	0.932	pathogenic	-0.437	Destabilizing	0.316	N	0.345	neutral	None	None	None	None	N
D/Y	0.3815	ambiguous	0.3385	benign	-0.232	Destabilizing	0.039	N	0.375	neutral	N	0.47336875	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.