TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2302	7129;7130;7131	chr2:178774360;178774359;178774358	chr2:179639087;179639086;179639085
N2AB	2302	7129;7130;7131	chr2:178774360;178774359;178774358	chr2:179639087;179639086;179639085
N2A	2302	7129;7130;7131	chr2:178774360;178774359;178774358	chr2:179639087;179639086;179639085
N2B	2256	6991;6992;6993	chr2:178774360;178774359;178774358	chr2:179639087;179639086;179639085
Novex-1	2256	6991;6992;6993	chr2:178774360;178774359;178774358	chr2:179639087;179639086;179639085
Novex-2	2256	6991;6992;6993	chr2:178774360;178774359;178774358	chr2:179639087;179639086;179639085
Novex-3	2302	7129;7130;7131	chr2:178774360;178774359;178774358	chr2:179639087;179639086;179639085

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-12
• Domain position: 36
• Structural Position: 51
• Q(SASA): 0.3912
• 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	None	None	0.295	D	0.505	0.163	0.461845970543	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	0.1831	likely_benign	0.1724	benign	-0.767	Destabilizing	0.007	N	0.312	neutral	None	None	None	None	N
N/C	0.198	likely_benign	0.1854	benign	0.235	Stabilizing	0.864	D	0.447	neutral	None	None	None	None	N
N/D	0.0879	likely_benign	0.0849	benign	-0.273	Destabilizing	None	N	0.095	neutral	N	0.441182261	None	None	N
N/E	0.2332	likely_benign	0.2223	benign	-0.226	Destabilizing	None	N	0.087	neutral	None	None	None	None	N
N/F	0.5511	ambiguous	0.5347	ambiguous	-0.684	Destabilizing	0.628	D	0.481	neutral	None	None	None	None	N
N/G	0.111	likely_benign	0.1083	benign	-1.061	Destabilizing	None	N	0.085	neutral	None	None	None	None	N
N/H	0.0915	likely_benign	0.0878	benign	-0.993	Destabilizing	0.295	N	0.314	neutral	D	0.614165922	None	None	N
N/I	0.4105	ambiguous	0.3793	ambiguous	-0.036	Destabilizing	0.295	N	0.505	neutral	D	0.615427103	None	None	N
N/K	0.1259	likely_benign	0.1214	benign	-0.345	Destabilizing	None	N	0.08	neutral	N	0.506045531	None	None	N
N/L	0.2675	likely_benign	0.2533	benign	-0.036	Destabilizing	0.072	N	0.477	neutral	None	None	None	None	N
N/M	0.3624	ambiguous	0.3484	ambiguous	0.415	Stabilizing	0.628	D	0.446	neutral	None	None	None	None	N
N/P	0.874	likely_pathogenic	0.8619	pathogenic	-0.251	Destabilizing	0.136	N	0.481	neutral	None	None	None	None	N
N/Q	0.1711	likely_benign	0.1628	benign	-0.723	Destabilizing	0.038	N	0.219	neutral	None	None	None	None	N
N/R	0.1534	likely_benign	0.1487	benign	-0.392	Destabilizing	0.038	N	0.205	neutral	None	None	None	None	N
N/S	0.0804	likely_benign	0.0762	benign	-0.674	Destabilizing	0.005	N	0.169	neutral	D	0.610895074	None	None	N
N/T	0.2099	likely_benign	0.1922	benign	-0.455	Destabilizing	0.024	N	0.193	neutral	D	0.614165922	None	None	N
N/V	0.3659	ambiguous	0.3382	benign	-0.251	Destabilizing	0.072	N	0.515	neutral	None	None	None	None	N
N/W	0.6679	likely_pathogenic	0.6594	pathogenic	-0.542	Destabilizing	0.864	D	0.449	neutral	None	None	None	None	N
N/Y	0.194	likely_benign	0.1859	benign	-0.358	Destabilizing	0.295	N	0.461	neutral	D	0.615427103	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.