TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20032	60319;60320;60321	chr2:178591725;178591724;178591723	chr2:179456452;179456451;179456450
N2AB	18391	55396;55397;55398	chr2:178591725;178591724;178591723	chr2:179456452;179456451;179456450
N2A	17464	52615;52616;52617	chr2:178591725;178591724;178591723	chr2:179456452;179456451;179456450
N2B	10967	33124;33125;33126	chr2:178591725;178591724;178591723	chr2:179456452;179456451;179456450
Novex-1	11092	33499;33500;33501	chr2:178591725;178591724;178591723	chr2:179456452;179456451;179456450
Novex-2	11159	33700;33701;33702	chr2:178591725;178591724;178591723	chr2:179456452;179456451;179456450
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-33
• Domain position: 56
• Structural Position: 88
• Q(SASA): 0.6005
• 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	rs1230376061	None	None	N	0.083	0.1	0.0846915920261	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/D	rs1230376061	None	None	N	0.083	0.1	0.0846915920261	gnomAD-4.0.0	3.09934E-06	None	None	None	None	N	None	0	5.00484E-05	None	0	0	None	0	0	1.69554E-06	0	0
N/I	None	None	None	N	0.156	0.252	0.36355261348	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1339	likely_benign	0.1333	benign	-0.393	Destabilizing	0.015	N	0.185	neutral	None	None	None	None	N
N/C	0.2785	likely_benign	0.3022	benign	0.021	Stabilizing	0.781	D	0.309	neutral	None	None	None	None	N
N/D	0.0842	likely_benign	0.0866	benign	0.103	Stabilizing	None	N	0.083	neutral	N	0.390938779	None	None	N
N/E	0.2011	likely_benign	0.2108	benign	0.134	Stabilizing	None	N	0.074	neutral	None	None	None	None	N
N/F	0.4507	ambiguous	0.4721	ambiguous	-0.68	Destabilizing	0.142	N	0.43	neutral	None	None	None	None	N
N/G	0.1725	likely_benign	0.1764	benign	-0.608	Destabilizing	0.064	N	0.127	neutral	None	None	None	None	N
N/H	0.1028	likely_benign	0.1067	benign	-0.415	Destabilizing	0.47	N	0.231	neutral	N	0.450872517	None	None	N
N/I	0.1914	likely_benign	0.2079	benign	0.1	Stabilizing	None	N	0.156	neutral	N	0.420763041	None	None	N
N/K	0.1841	likely_benign	0.1913	benign	0.082	Stabilizing	0.025	N	0.135	neutral	N	0.437308574	None	None	N
N/L	0.2003	likely_benign	0.2031	benign	0.1	Stabilizing	0.002	N	0.206	neutral	None	None	None	None	N
N/M	0.2539	likely_benign	0.2496	benign	0.037	Stabilizing	0.006	N	0.171	neutral	None	None	None	None	N
N/P	0.589	likely_pathogenic	0.6379	pathogenic	-0.037	Destabilizing	0.251	N	0.362	neutral	None	None	None	None	N
N/Q	0.2046	likely_benign	0.204	benign	-0.374	Destabilizing	0.076	N	0.143	neutral	None	None	None	None	N
N/R	0.2302	likely_benign	0.2302	benign	0.125	Stabilizing	0.142	N	0.152	neutral	None	None	None	None	N
N/S	0.0686	likely_benign	0.0667	benign	-0.347	Destabilizing	0.025	N	0.15	neutral	N	0.401289059	None	None	N
N/T	0.0939	likely_benign	0.0936	benign	-0.151	Destabilizing	0.049	N	0.149	neutral	N	0.418122593	None	None	N
N/V	0.1726	likely_benign	0.184	benign	-0.037	Destabilizing	None	N	0.187	neutral	None	None	None	None	N
N/W	0.6952	likely_pathogenic	0.7188	pathogenic	-0.679	Destabilizing	0.931	D	0.317	neutral	None	None	None	None	N
N/Y	0.1695	likely_benign	0.1914	benign	-0.37	Destabilizing	0.202	N	0.395	neutral	N	0.470325069	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.