TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9349	28270;28271;28272	chr2:178711191;178711190;178711189	chr2:179575918;179575917;179575916
N2AB	9032	27319;27320;27321	chr2:178711191;178711190;178711189	chr2:179575918;179575917;179575916
N2A	8105	24538;24539;24540	chr2:178711191;178711190;178711189	chr2:179575918;179575917;179575916
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-79
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.3444
• 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
T/A	None	None	None	None	0.116	0.111	0.198526703765	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
T/I	rs749966898	0.077	None	None	0.218	0.118	0.285698343383	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
T/I	rs749966898	0.077	None	None	0.218	0.118	0.285698343383	gnomAD-4.0.0	4.77332E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71634E-06	0	3.02352E-05

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
T/A	0.1042	likely_benign	0.1048	benign	-1.239	Destabilizing	None	N	0.116	neutral	None	None	None	None	N
T/C	0.5007	ambiguous	0.4327	ambiguous	-0.703	Destabilizing	0.555	D	0.578	neutral	None	None	None	None	N
T/D	0.6233	likely_pathogenic	0.6301	pathogenic	-0.613	Destabilizing	0.38	N	0.588	neutral	None	None	None	None	N
T/E	0.4573	ambiguous	0.4819	ambiguous	-0.523	Destabilizing	0.149	N	0.557	neutral	None	None	None	None	N
T/F	0.2601	likely_benign	0.2673	benign	-1.187	Destabilizing	0.38	N	0.63	neutral	None	None	None	None	N
T/G	0.3136	likely_benign	0.3086	benign	-1.582	Destabilizing	0.081	N	0.563	neutral	None	None	None	None	N
T/H	0.3156	likely_benign	0.3314	benign	-1.801	Destabilizing	0.935	D	0.608	neutral	None	None	None	None	N
T/I	0.1932	likely_benign	0.1976	benign	-0.377	Destabilizing	None	N	0.218	neutral	None	None	None	None	N
T/K	0.2624	likely_benign	0.2864	benign	-0.706	Destabilizing	0.117	N	0.557	neutral	None	None	None	None	N
T/L	0.1141	likely_benign	0.1265	benign	-0.377	Destabilizing	0.005	N	0.329	neutral	None	None	None	None	N
T/M	0.0907	likely_benign	0.0978	benign	-0.058	Destabilizing	0.007	N	0.353	neutral	None	None	None	None	N
T/N	0.1882	likely_benign	0.1937	benign	-0.95	Destabilizing	0.555	D	0.534	neutral	None	None	None	None	N
T/P	0.2717	likely_benign	0.3085	benign	-0.632	Destabilizing	0.317	N	0.597	neutral	None	None	None	None	N
T/Q	0.286	likely_benign	0.3171	benign	-0.943	Destabilizing	0.555	D	0.596	neutral	None	None	None	None	N
T/R	0.2083	likely_benign	0.2358	benign	-0.672	Destabilizing	0.317	N	0.597	neutral	None	None	None	None	N
T/S	0.1366	likely_benign	0.1384	benign	-1.279	Destabilizing	0.027	N	0.466	neutral	None	None	None	None	N
T/V	0.1629	likely_benign	0.163	benign	-0.632	Destabilizing	0.005	N	0.296	neutral	None	None	None	None	N
T/W	0.6378	likely_pathogenic	0.668	pathogenic	-1.139	Destabilizing	0.935	D	0.628	neutral	None	None	None	None	N
T/Y	0.2832	likely_benign	0.2964	benign	-0.879	Destabilizing	0.555	D	0.619	neutral	None	None	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.