TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24305	73138;73139;73140	chr2:178573219;178573218;178573217	chr2:179437946;179437945;179437944
N2AB	22664	68215;68216;68217	chr2:178573219;178573218;178573217	chr2:179437946;179437945;179437944
N2A	21737	65434;65435;65436	chr2:178573219;178573218;178573217	chr2:179437946;179437945;179437944
N2B	15240	45943;45944;45945	chr2:178573219;178573218;178573217	chr2:179437946;179437945;179437944
Novex-1	15365	46318;46319;46320	chr2:178573219;178573218;178573217	chr2:179437946;179437945;179437944
Novex-2	15432	46519;46520;46521	chr2:178573219;178573218;178573217	chr2:179437946;179437945;179437944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-64
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.3011
• 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
I/S	None	None	0.175	N	0.561	0.164	0.701967312675	gnomAD-4.0.0	1.60834E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.05064E-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
I/A	0.303	likely_benign	0.2099	benign	-1.277	Destabilizing	0.025	N	0.441	neutral	None	None	None	None	N
I/C	0.5001	ambiguous	0.4176	ambiguous	-0.749	Destabilizing	0.667	D	0.549	neutral	None	None	None	None	N
I/D	0.6342	likely_pathogenic	0.4928	ambiguous	-0.561	Destabilizing	0.22	N	0.595	neutral	None	None	None	None	N
I/E	0.5234	ambiguous	0.3826	ambiguous	-0.626	Destabilizing	0.124	N	0.572	neutral	None	None	None	None	N
I/F	0.143	likely_benign	0.1106	benign	-1.101	Destabilizing	0.096	N	0.523	neutral	N	0.487038387	None	None	N
I/G	0.5596	ambiguous	0.4117	ambiguous	-1.517	Destabilizing	0.364	N	0.555	neutral	None	None	None	None	N
I/H	0.4457	ambiguous	0.3363	benign	-0.669	Destabilizing	0.667	D	0.585	neutral	None	None	None	None	N
I/K	0.3452	ambiguous	0.2429	benign	-0.668	Destabilizing	0.124	N	0.57	neutral	None	None	None	None	N
I/L	0.0881	likely_benign	0.0772	benign	-0.734	Destabilizing	None	N	0.185	neutral	N	0.409230964	None	None	N
I/M	0.1108	likely_benign	0.0912	benign	-0.506	Destabilizing	0.427	N	0.565	neutral	N	0.492502922	None	None	N
I/N	0.2236	likely_benign	0.157	benign	-0.382	Destabilizing	0.602	D	0.593	neutral	N	0.49107877	None	None	N
I/P	0.4181	ambiguous	0.3299	benign	-0.882	Destabilizing	0.859	D	0.597	neutral	None	None	None	None	N
I/Q	0.3846	ambiguous	0.2783	benign	-0.652	Destabilizing	0.011	N	0.533	neutral	None	None	None	None	N
I/R	0.291	likely_benign	0.2091	benign	-0.016	Destabilizing	0.22	N	0.592	neutral	None	None	None	None	N
I/S	0.2772	likely_benign	0.201	benign	-0.962	Destabilizing	0.175	N	0.561	neutral	N	0.495407154	None	None	N
I/T	0.2218	likely_benign	0.1528	benign	-0.914	Destabilizing	0.081	N	0.498	neutral	N	0.454099249	None	None	N
I/V	0.0673	likely_benign	0.0584	benign	-0.882	Destabilizing	None	N	0.199	neutral	N	0.390549203	None	None	N
I/W	0.718	likely_pathogenic	0.6399	pathogenic	-1.067	Destabilizing	0.958	D	0.591	neutral	None	None	None	None	N
I/Y	0.4132	ambiguous	0.336	benign	-0.846	Destabilizing	0.667	D	0.573	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.