TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27878	83857;83858;83859	chr2:178562500;178562499;178562498	chr2:179427227;179427226;179427225
N2AB	26237	78934;78935;78936	chr2:178562500;178562499;178562498	chr2:179427227;179427226;179427225
N2A	25310	76153;76154;76155	chr2:178562500;178562499;178562498	chr2:179427227;179427226;179427225
N2B	18813	56662;56663;56664	chr2:178562500;178562499;178562498	chr2:179427227;179427226;179427225
Novex-1	18938	57037;57038;57039	chr2:178562500;178562499;178562498	chr2:179427227;179427226;179427225
Novex-2	19005	57238;57239;57240	chr2:178562500;178562499;178562498	chr2:179427227;179427226;179427225
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: Fn3-91
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.5062
• 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/D	None	None	0.048	N	0.393	0.156	0.208816687407	gnomAD-4.0.0	7.20193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.87501E-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
N/A	0.2651	likely_benign	0.2499	benign	-0.653	Destabilizing	0.004	N	0.36	neutral	None	None	None	None	N
N/C	0.3184	likely_benign	0.3046	benign	0.195	Stabilizing	0.863	D	0.48	neutral	None	None	None	None	N
N/D	0.129	likely_benign	0.1438	benign	-0.537	Destabilizing	0.048	N	0.393	neutral	N	0.461318797	None	None	N
N/E	0.2894	likely_benign	0.3178	benign	-0.558	Destabilizing	0.101	N	0.336	neutral	None	None	None	None	N
N/F	0.5403	ambiguous	0.5255	ambiguous	-1.014	Destabilizing	0.856	D	0.456	neutral	None	None	None	None	N
N/G	0.3045	likely_benign	0.286	benign	-0.836	Destabilizing	0.104	N	0.375	neutral	None	None	None	None	N
N/H	0.1025	likely_benign	0.0989	benign	-0.905	Destabilizing	0.001	N	0.136	neutral	N	0.475885605	None	None	N
N/I	0.3333	likely_benign	0.3418	ambiguous	-0.243	Destabilizing	0.454	N	0.467	neutral	N	0.487488484	None	None	N
N/K	0.2232	likely_benign	0.2538	benign	0.015	Stabilizing	0.241	N	0.367	neutral	N	0.486139884	None	None	N
N/L	0.2827	likely_benign	0.2826	benign	-0.243	Destabilizing	0.239	N	0.424	neutral	None	None	None	None	N
N/M	0.3016	likely_benign	0.2902	benign	0.473	Stabilizing	0.962	D	0.423	neutral	None	None	None	None	N
N/P	0.8893	likely_pathogenic	0.8835	pathogenic	-0.354	Destabilizing	0.191	N	0.444	neutral	None	None	None	None	N
N/Q	0.2377	likely_benign	0.2426	benign	-0.717	Destabilizing	0.524	D	0.413	neutral	None	None	None	None	N
N/R	0.2706	likely_benign	0.2986	benign	0.187	Stabilizing	0.456	N	0.403	neutral	None	None	None	None	N
N/S	0.0919	likely_benign	0.0879	benign	-0.363	Destabilizing	None	N	0.16	neutral	N	0.421490972	None	None	N
N/T	0.1117	likely_benign	0.1062	benign	-0.241	Destabilizing	0.038	N	0.357	neutral	N	0.393320149	None	None	N
N/V	0.3043	likely_benign	0.3065	benign	-0.354	Destabilizing	0.084	N	0.449	neutral	None	None	None	None	N
N/W	0.7372	likely_pathogenic	0.7381	pathogenic	-0.88	Destabilizing	0.986	D	0.569	neutral	None	None	None	None	N
N/Y	0.1705	likely_benign	0.1725	benign	-0.627	Destabilizing	0.689	D	0.443	neutral	N	0.487488484	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.