TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26502	79729;79730;79731	chr2:178566628;178566627;178566626	chr2:179431355;179431354;179431353
N2AB	24861	74806;74807;74808	chr2:178566628;178566627;178566626	chr2:179431355;179431354;179431353
N2A	23934	72025;72026;72027	chr2:178566628;178566627;178566626	chr2:179431355;179431354;179431353
N2B	17437	52534;52535;52536	chr2:178566628;178566627;178566626	chr2:179431355;179431354;179431353
Novex-1	17562	52909;52910;52911	chr2:178566628;178566627;178566626	chr2:179431355;179431354;179431353
Novex-2	17629	53110;53111;53112	chr2:178566628;178566627;178566626	chr2:179431355;179431354;179431353
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: Fn3-81
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4248
• 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	rs1423556952	-0.106	None	N	0.059	0.157	0.119812018005	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
N/D	rs1423556952	-0.106	None	N	0.059	0.157	0.119812018005	gnomAD-4.0.0	9.56319E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.71535E-05	0	0
N/T	rs1705971546	None	0.062	N	0.271	0.052	0.115124310173	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07641E-04	0
N/T	rs1705971546	None	0.062	N	0.271	0.052	0.115124310173	gnomAD-4.0.0	6.57618E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07641E-04	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	0.191	likely_benign	0.1522	benign	-0.761	Destabilizing	0.035	N	0.305	neutral	None	None	None	None	N
N/C	0.1804	likely_benign	0.1483	benign	-0.048	Destabilizing	0.824	D	0.381	neutral	None	None	None	None	N
N/D	0.1021	likely_benign	0.0923	benign	-0.96	Destabilizing	None	N	0.059	neutral	N	0.442194319	None	None	N
N/E	0.2938	likely_benign	0.2459	benign	-0.933	Destabilizing	0.035	N	0.281	neutral	None	None	None	None	N
N/F	0.4129	ambiguous	0.3455	ambiguous	-0.937	Destabilizing	0.555	D	0.386	neutral	None	None	None	None	N
N/G	0.2293	likely_benign	0.1931	benign	-1.003	Destabilizing	0.035	N	0.323	neutral	None	None	None	None	N
N/H	0.0929	likely_benign	0.084	benign	-0.925	Destabilizing	0.484	N	0.407	neutral	N	0.482888935	None	None	N
N/I	0.2831	likely_benign	0.2371	benign	-0.18	Destabilizing	0.317	N	0.403	neutral	N	0.491932256	None	None	N
N/K	0.2746	likely_benign	0.2176	benign	-0.157	Destabilizing	0.062	N	0.294	neutral	N	0.471055788	None	None	N
N/L	0.2593	likely_benign	0.2144	benign	-0.18	Destabilizing	0.149	N	0.401	neutral	None	None	None	None	N
N/M	0.2831	likely_benign	0.2301	benign	0.485	Stabilizing	0.935	D	0.355	neutral	None	None	None	None	N
N/P	0.8788	likely_pathogenic	0.8546	pathogenic	-0.347	Destabilizing	0.38	N	0.384	neutral	None	None	None	None	N
N/Q	0.2611	likely_benign	0.215	benign	-1.006	Destabilizing	0.38	N	0.369	neutral	None	None	None	None	N
N/R	0.3211	likely_benign	0.2647	benign	0.029	Stabilizing	0.38	N	0.365	neutral	None	None	None	None	N
N/S	0.0706	likely_benign	0.0646	benign	-0.692	Destabilizing	None	N	0.076	neutral	N	0.398056752	None	None	N
N/T	0.0836	likely_benign	0.0725	benign	-0.506	Destabilizing	0.062	N	0.271	neutral	N	0.428606159	None	None	N
N/V	0.265	likely_benign	0.2212	benign	-0.347	Destabilizing	0.38	N	0.411	neutral	None	None	None	None	N
N/W	0.6866	likely_pathogenic	0.6328	pathogenic	-0.742	Destabilizing	0.935	D	0.543	neutral	None	None	None	None	N
N/Y	0.1206	likely_benign	0.1114	benign	-0.489	Destabilizing	0.484	N	0.365	neutral	N	0.469055061	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.