TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16804	50635;50636;50637	chr2:178611899;178611898;178611897	chr2:179476626;179476625;179476624
N2AB	15163	45712;45713;45714	chr2:178611899;178611898;178611897	chr2:179476626;179476625;179476624
N2A	14236	42931;42932;42933	chr2:178611899;178611898;178611897	chr2:179476626;179476625;179476624
N2B	7739	23440;23441;23442	chr2:178611899;178611898;178611897	chr2:179476626;179476625;179476624
Novex-1	7864	23815;23816;23817	chr2:178611899;178611898;178611897	chr2:179476626;179476625;179476624
Novex-2	7931	24016;24017;24018	chr2:178611899;178611898;178611897	chr2:179476626;179476625;179476624
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-10
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.7338
• Predicted PPI site: I

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/S	None	None	0.999	N	0.517	0.297	0.28297238246	gnomAD-4.0.0	1.59361E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86198E-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
T/A	0.4363	ambiguous	0.4085	ambiguous	-1.144	Destabilizing	0.999	D	0.495	neutral	N	0.481254514	None	None	I
T/C	0.8457	likely_pathogenic	0.8419	pathogenic	-0.662	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	I
T/D	0.9516	likely_pathogenic	0.9413	pathogenic	-0.609	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	I
T/E	0.9254	likely_pathogenic	0.9139	pathogenic	-0.444	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	I
T/F	0.8967	likely_pathogenic	0.8906	pathogenic	-0.826	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
T/G	0.7507	likely_pathogenic	0.7541	pathogenic	-1.538	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	I
T/H	0.8841	likely_pathogenic	0.861	pathogenic	-1.488	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
T/I	0.7362	likely_pathogenic	0.7119	pathogenic	-0.121	Destabilizing	1.0	D	0.626	neutral	N	0.470567161	None	None	I
T/K	0.8779	likely_pathogenic	0.8504	pathogenic	-0.32	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
T/L	0.5338	ambiguous	0.5161	ambiguous	-0.121	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	I
T/M	0.4119	ambiguous	0.3565	ambiguous	-0.134	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	I
T/N	0.6217	likely_pathogenic	0.6128	pathogenic	-0.797	Destabilizing	1.0	D	0.691	prob.neutral	N	0.466256289	None	None	I
T/P	0.7715	likely_pathogenic	0.733	pathogenic	-0.431	Destabilizing	1.0	D	0.62	neutral	N	0.515216227	None	None	I
T/Q	0.8695	likely_pathogenic	0.8528	pathogenic	-0.672	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
T/R	0.8555	likely_pathogenic	0.8353	pathogenic	-0.412	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
T/S	0.5055	ambiguous	0.4732	ambiguous	-1.176	Destabilizing	0.999	D	0.517	neutral	N	0.475660437	None	None	I
T/V	0.5229	ambiguous	0.5066	ambiguous	-0.431	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	I
T/W	0.9768	likely_pathogenic	0.9755	pathogenic	-0.817	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
T/Y	0.9151	likely_pathogenic	0.9133	pathogenic	-0.487	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I

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.