TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26447	79564;79565;79566	chr2:178566793;178566792;178566791	chr2:179431520;179431519;179431518
N2AB	24806	74641;74642;74643	chr2:178566793;178566792;178566791	chr2:179431520;179431519;179431518
N2A	23879	71860;71861;71862	chr2:178566793;178566792;178566791	chr2:179431520;179431519;179431518
N2B	17382	52369;52370;52371	chr2:178566793;178566792;178566791	chr2:179431520;179431519;179431518
Novex-1	17507	52744;52745;52746	chr2:178566793;178566792;178566791	chr2:179431520;179431519;179431518
Novex-2	17574	52945;52946;52947	chr2:178566793;178566792;178566791	chr2:179431520;179431519;179431518
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-80
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.5206
• 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
R/G	None	None	0.892	N	0.637	0.358	0.539567288477	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	2.77624E-05	None	0	0	0	0	0
R/K	None	None	0.025	N	0.308	0.143	0.202086224978	gnomAD-4.0.0	4.77661E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71762E-06	0	3.02572E-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
R/A	0.9654	likely_pathogenic	0.9718	pathogenic	-0.521	Destabilizing	0.845	D	0.61	neutral	None	None	None	None	N
R/C	0.7485	likely_pathogenic	0.7733	pathogenic	-0.471	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
R/D	0.9903	likely_pathogenic	0.9932	pathogenic	-0.104	Destabilizing	0.975	D	0.694	prob.neutral	None	None	None	None	N
R/E	0.9534	likely_pathogenic	0.9635	pathogenic	-0.037	Destabilizing	0.845	D	0.561	neutral	None	None	None	None	N
R/F	0.9747	likely_pathogenic	0.979	pathogenic	-0.719	Destabilizing	0.996	D	0.713	prob.delet.	None	None	None	None	N
R/G	0.9475	likely_pathogenic	0.9582	pathogenic	-0.747	Destabilizing	0.892	D	0.637	neutral	N	0.494664053	None	None	N
R/H	0.4887	ambiguous	0.538	ambiguous	-1.133	Destabilizing	0.987	D	0.647	neutral	None	None	None	None	N
R/I	0.9057	likely_pathogenic	0.9196	pathogenic	0.054	Stabilizing	0.983	D	0.718	prob.delet.	N	0.472152025	None	None	N
R/K	0.2812	likely_benign	0.3321	benign	-0.515	Destabilizing	0.025	N	0.308	neutral	N	0.442154246	None	None	N
R/L	0.8354	likely_pathogenic	0.8563	pathogenic	0.054	Stabilizing	0.916	D	0.637	neutral	None	None	None	None	N
R/M	0.9109	likely_pathogenic	0.921	pathogenic	-0.116	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
R/N	0.9841	likely_pathogenic	0.9874	pathogenic	-0.001	Destabilizing	0.975	D	0.631	neutral	None	None	None	None	N
R/P	0.967	likely_pathogenic	0.9741	pathogenic	-0.117	Destabilizing	0.987	D	0.715	prob.delet.	None	None	None	None	N
R/Q	0.5348	ambiguous	0.5723	pathogenic	-0.263	Destabilizing	0.975	D	0.629	neutral	None	None	None	None	N
R/S	0.9811	likely_pathogenic	0.9857	pathogenic	-0.638	Destabilizing	0.892	D	0.659	neutral	N	0.520076312	None	None	N
R/T	0.9328	likely_pathogenic	0.9542	pathogenic	-0.424	Destabilizing	0.967	D	0.683	prob.neutral	N	0.453096385	None	None	N
R/V	0.9181	likely_pathogenic	0.9335	pathogenic	-0.117	Destabilizing	0.975	D	0.719	prob.delet.	None	None	None	None	N
R/W	0.7132	likely_pathogenic	0.7408	pathogenic	-0.549	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
R/Y	0.9271	likely_pathogenic	0.9334	pathogenic	-0.182	Destabilizing	0.996	D	0.719	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.