TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2571	7936;7937;7938	chr2:178773253;178773252;178773251	chr2:179637980;179637979;179637978
N2AB	2571	7936;7937;7938	chr2:178773253;178773252;178773251	chr2:179637980;179637979;179637978
N2A	2571	7936;7937;7938	chr2:178773253;178773252;178773251	chr2:179637980;179637979;179637978
N2B	2525	7798;7799;7800	chr2:178773253;178773252;178773251	chr2:179637980;179637979;179637978
Novex-1	2525	7798;7799;7800	chr2:178773253;178773252;178773251	chr2:179637980;179637979;179637978
Novex-2	2525	7798;7799;7800	chr2:178773253;178773252;178773251	chr2:179637980;179637979;179637978
Novex-3	2571	7936;7937;7938	chr2:178773253;178773252;178773251	chr2:179637980;179637979;179637978

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-15
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.5466
• 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
E/K	rs149660690	-0.117	0.029	N	0.314	0.203	None	gnomAD-2.1.1	5.68E-05	None	None	None	None	N	None	6.06208E-04	0	None	0	0	None	0	None	0	7.77E-06	0
E/K	rs149660690	-0.117	0.029	N	0.314	0.203	None	gnomAD-3.1.2	1.6442E-04	None	None	None	None	N	None	5.5577E-04	1.31027E-04	0	0	0	None	0	0	0	0	0
E/K	rs149660690	-0.117	0.029	N	0.314	0.203	None	1000 genomes	1.19808E-03	None	None	None	None	N	None	4.5E-03	0	None	None	0	0	None	None	None	0	None
E/K	rs149660690	-0.117	0.029	N	0.314	0.203	None	gnomAD-4.0.0	3.34608E-05	None	None	None	None	N	None	5.33476E-04	3.33489E-05	None	0	0	None	0	0	4.23752E-06	0	1.12011E-04
E/V	None	None	0.029	N	0.39	0.24	0.484037581386	gnomAD-4.0.0	1.59096E-06	None	None	None	None	N	None	0	0	None	0	2.77778E-05	None	0	0	0	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
E/A	0.1249	likely_benign	0.121	benign	-0.505	Destabilizing	0.012	N	0.318	neutral	N	0.511476828	None	None	N
E/C	0.8195	likely_pathogenic	0.8105	pathogenic	-0.312	Destabilizing	0.864	D	0.389	neutral	None	None	None	None	N
E/D	0.1783	likely_benign	0.1697	benign	-0.442	Destabilizing	0.024	N	0.312	neutral	D	0.583316423	None	None	N
E/F	0.7276	likely_pathogenic	0.6979	pathogenic	-0.204	Destabilizing	0.214	N	0.412	neutral	None	None	None	None	N
E/G	0.2087	likely_benign	0.1888	benign	-0.733	Destabilizing	None	N	0.192	neutral	D	0.653133125	None	None	N
E/H	0.5093	ambiguous	0.4984	ambiguous	0.05	Stabilizing	0.356	N	0.359	neutral	None	None	None	None	N
E/I	0.2346	likely_benign	0.2221	benign	0.074	Stabilizing	0.12	N	0.419	neutral	None	None	None	None	N
E/K	0.1566	likely_benign	0.1492	benign	0.031	Stabilizing	0.029	N	0.314	neutral	N	0.503019816	None	None	N
E/L	0.3097	likely_benign	0.2995	benign	0.074	Stabilizing	None	N	0.241	neutral	None	None	None	None	N
E/M	0.3654	ambiguous	0.3519	ambiguous	0.1	Stabilizing	0.214	N	0.387	neutral	None	None	None	None	N
E/N	0.2701	likely_benign	0.2528	benign	-0.374	Destabilizing	0.072	N	0.339	neutral	None	None	None	None	N
E/P	0.2345	likely_benign	0.2372	benign	-0.099	Destabilizing	None	N	0.133	neutral	None	None	None	None	N
E/Q	0.1411	likely_benign	0.1393	benign	-0.301	Destabilizing	0.002	N	0.188	neutral	N	0.501624763	None	None	N
E/R	0.2784	likely_benign	0.2744	benign	0.351	Stabilizing	0.072	N	0.336	neutral	None	None	None	None	N
E/S	0.241	likely_benign	0.227	benign	-0.542	Destabilizing	0.038	N	0.271	neutral	None	None	None	None	N
E/T	0.2052	likely_benign	0.1916	benign	-0.353	Destabilizing	0.072	N	0.343	neutral	None	None	None	None	N
E/V	0.1453	likely_benign	0.1374	benign	-0.099	Destabilizing	0.029	N	0.39	neutral	N	0.512413766	None	None	N
E/W	0.8891	likely_pathogenic	0.8774	pathogenic	-0.003	Destabilizing	0.864	D	0.418	neutral	None	None	None	None	N
E/Y	0.6048	likely_pathogenic	0.5743	pathogenic	0.035	Stabilizing	0.628	D	0.397	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.