TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1575	4948;4949;4950	chr2:178777240;178777239;178777238	chr2:179641967;179641966;179641965
N2AB	1575	4948;4949;4950	chr2:178777240;178777239;178777238	chr2:179641967;179641966;179641965
N2A	1575	4948;4949;4950	chr2:178777240;178777239;178777238	chr2:179641967;179641966;179641965
N2B	1529	4810;4811;4812	chr2:178777240;178777239;178777238	chr2:179641967;179641966;179641965
Novex-1	1529	4810;4811;4812	chr2:178777240;178777239;178777238	chr2:179641967;179641966;179641965
Novex-2	1529	4810;4811;4812	chr2:178777240;178777239;178777238	chr2:179641967;179641966;179641965
Novex-3	1575	4948;4949;4950	chr2:178777240;178777239;178777238	chr2:179641967;179641966;179641965

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-7
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1033
• 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
M/I	None	None	0.316	N	0.407	0.314	0.380901646489	gnomAD-4.0.0	1.5907E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85691E-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
M/A	0.957	likely_pathogenic	0.936	pathogenic	-2.238	Highly Destabilizing	0.85	D	0.553	neutral	None	None	None	None	N
M/C	0.97	likely_pathogenic	0.9538	pathogenic	-2.152	Highly Destabilizing	0.993	D	0.737	prob.delet.	None	None	None	None	N
M/D	0.9992	likely_pathogenic	0.9991	pathogenic	-1.847	Destabilizing	0.993	D	0.802	deleterious	None	None	None	None	N
M/E	0.9916	likely_pathogenic	0.9907	pathogenic	-1.633	Destabilizing	0.977	D	0.742	deleterious	None	None	None	None	N
M/F	0.611	likely_pathogenic	0.5197	ambiguous	-0.953	Destabilizing	0.872	D	0.571	neutral	None	None	None	None	N
M/G	0.9874	likely_pathogenic	0.9824	pathogenic	-2.674	Highly Destabilizing	0.977	D	0.747	deleterious	None	None	None	None	N
M/H	0.9924	likely_pathogenic	0.9897	pathogenic	-1.954	Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
M/I	0.693	likely_pathogenic	0.5803	pathogenic	-0.985	Destabilizing	0.316	N	0.407	neutral	N	0.489508503	None	None	N
M/K	0.9606	likely_pathogenic	0.9516	pathogenic	-1.296	Destabilizing	0.969	D	0.627	neutral	D	0.603915509	None	None	N
M/L	0.2119	likely_benign	0.18	benign	-0.985	Destabilizing	0.002	N	0.229	neutral	N	0.356218586	None	None	N
M/N	0.9933	likely_pathogenic	0.9913	pathogenic	-1.674	Destabilizing	0.993	D	0.778	deleterious	None	None	None	None	N
M/P	0.9993	likely_pathogenic	0.999	pathogenic	-1.387	Destabilizing	0.993	D	0.779	deleterious	None	None	None	None	N
M/Q	0.9593	likely_pathogenic	0.9529	pathogenic	-1.442	Destabilizing	0.993	D	0.651	neutral	None	None	None	None	N
M/R	0.9659	likely_pathogenic	0.9568	pathogenic	-1.245	Destabilizing	0.969	D	0.722	prob.delet.	D	0.603915509	None	None	N
M/S	0.9897	likely_pathogenic	0.9857	pathogenic	-2.231	Highly Destabilizing	0.977	D	0.623	neutral	None	None	None	None	N
M/T	0.963	likely_pathogenic	0.9443	pathogenic	-1.887	Destabilizing	0.912	D	0.613	neutral	D	0.562183336	None	None	N
M/V	0.3741	ambiguous	0.295	benign	-1.387	Destabilizing	0.316	N	0.399	neutral	N	0.50744401	None	None	N
M/W	0.9624	likely_pathogenic	0.9416	pathogenic	-1.109	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
M/Y	0.9403	likely_pathogenic	0.9167	pathogenic	-1.095	Destabilizing	0.993	D	0.731	prob.delet.	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.