TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5426	16501;16502;16503	chr2:178732900;178732899;178732898	chr2:179597627;179597626;179597625
N2AB	5109	15550;15551;15552	chr2:178732900;178732899;178732898	chr2:179597627;179597626;179597625
N2A	4182	12769;12770;12771	chr2:178732900;178732899;178732898	chr2:179597627;179597626;179597625
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-37
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.5743
• 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
N/I	rs761498812	-0.104	None	N	0.353	0.257	0.426787303895	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
N/I	rs761498812	-0.104	None	N	0.353	0.257	0.426787303895	gnomAD-4.0.0	1.59237E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85935E-06	0	0
N/S	rs761498812	-0.107	None	N	0.123	0.094	0.115124310173	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/S	rs761498812	-0.107	None	N	0.123	0.094	0.115124310173	gnomAD-4.0.0	1.59237E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43369E-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
N/A	0.1675	likely_benign	0.1793	benign	-0.904	Destabilizing	0.002	N	0.305	neutral	None	None	None	None	N
N/C	0.2423	likely_benign	0.2474	benign	0.083	Stabilizing	0.245	N	0.527	neutral	None	None	None	None	N
N/D	0.1336	likely_benign	0.1538	benign	-0.386	Destabilizing	0.007	N	0.324	neutral	N	0.453115893	None	None	N
N/E	0.266	likely_benign	0.323	benign	-0.376	Destabilizing	None	N	0.111	neutral	None	None	None	None	N
N/F	0.316	likely_benign	0.3554	ambiguous	-1.139	Destabilizing	0.044	N	0.598	neutral	None	None	None	None	N
N/G	0.275	likely_benign	0.2798	benign	-1.13	Destabilizing	0.009	N	0.268	neutral	None	None	None	None	N
N/H	0.091	likely_benign	0.0943	benign	-1.119	Destabilizing	0.196	N	0.405	neutral	N	0.472568446	None	None	N
N/I	0.1013	likely_benign	0.1115	benign	-0.37	Destabilizing	None	N	0.353	neutral	N	0.434087415	None	None	N
N/K	0.2038	likely_benign	0.2444	benign	-0.069	Destabilizing	None	N	0.109	neutral	N	0.422752914	None	None	N
N/L	0.1442	likely_benign	0.1555	benign	-0.37	Destabilizing	0.004	N	0.336	neutral	None	None	None	None	N
N/M	0.2186	likely_benign	0.2371	benign	0.333	Stabilizing	0.138	N	0.571	neutral	None	None	None	None	N
N/P	0.4207	ambiguous	0.4443	ambiguous	-0.522	Destabilizing	0.085	N	0.529	neutral	None	None	None	None	N
N/Q	0.237	likely_benign	0.2611	benign	-0.755	Destabilizing	0.044	N	0.353	neutral	None	None	None	None	N
N/R	0.2108	likely_benign	0.2502	benign	0.041	Stabilizing	0.022	N	0.337	neutral	None	None	None	None	N
N/S	0.0814	likely_benign	0.082	benign	-0.54	Destabilizing	None	N	0.123	neutral	N	0.443533618	None	None	N
N/T	0.1038	likely_benign	0.1091	benign	-0.362	Destabilizing	None	N	0.139	neutral	N	0.417309809	None	None	N
N/V	0.1252	likely_benign	0.1373	benign	-0.522	Destabilizing	None	N	0.306	neutral	None	None	None	None	N
N/W	0.6278	likely_pathogenic	0.6624	pathogenic	-0.939	Destabilizing	0.788	D	0.531	neutral	None	None	None	None	N
N/Y	0.1021	likely_benign	0.1133	benign	-0.723	Destabilizing	0.065	N	0.606	neutral	N	0.482708082	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.