TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21789	65590;65591;65592	chr2:178583817;178583816;178583815	chr2:179448544;179448543;179448542
N2AB	20148	60667;60668;60669	chr2:178583817;178583816;178583815	chr2:179448544;179448543;179448542
N2A	19221	57886;57887;57888	chr2:178583817;178583816;178583815	chr2:179448544;179448543;179448542
N2B	12724	38395;38396;38397	chr2:178583817;178583816;178583815	chr2:179448544;179448543;179448542
Novex-1	12849	38770;38771;38772	chr2:178583817;178583816;178583815	chr2:179448544;179448543;179448542
Novex-2	12916	38971;38972;38973	chr2:178583817;178583816;178583815	chr2:179448544;179448543;179448542
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: Fn3-46
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1019
• 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/T	rs2048319290	None	0.684	D	0.795	0.474	0.707130027437	gnomAD-4.0.0	1.12037E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.00997E-05	0	0
I/V	None	None	0.003	N	0.227	0.09	0.524166996187	gnomAD-4.0.0	1.60089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87223E-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
I/A	0.966	likely_pathogenic	0.9329	pathogenic	-2.04	Highly Destabilizing	0.373	N	0.735	prob.delet.	None	None	None	None	N
I/C	0.9624	likely_pathogenic	0.9292	pathogenic	-1.329	Destabilizing	0.996	D	0.773	deleterious	None	None	None	None	N
I/D	0.9923	likely_pathogenic	0.9874	pathogenic	-1.405	Destabilizing	0.984	D	0.835	deleterious	None	None	None	None	N
I/E	0.9806	likely_pathogenic	0.972	pathogenic	-1.299	Destabilizing	0.953	D	0.822	deleterious	None	None	None	None	N
I/F	0.779	likely_pathogenic	0.6336	pathogenic	-1.249	Destabilizing	0.884	D	0.784	deleterious	N	0.521409724	None	None	N
I/G	0.9892	likely_pathogenic	0.9792	pathogenic	-2.474	Highly Destabilizing	0.953	D	0.825	deleterious	None	None	None	None	N
I/H	0.98	likely_pathogenic	0.9601	pathogenic	-1.626	Destabilizing	0.996	D	0.784	deleterious	None	None	None	None	N
I/K	0.954	likely_pathogenic	0.9326	pathogenic	-1.362	Destabilizing	0.953	D	0.827	deleterious	None	None	None	None	N
I/L	0.2434	likely_benign	0.1636	benign	-0.862	Destabilizing	0.001	N	0.203	neutral	N	0.516926938	None	None	N
I/M	0.352	ambiguous	0.2578	benign	-0.736	Destabilizing	0.884	D	0.733	prob.delet.	D	0.530692569	None	None	N
I/N	0.8768	likely_pathogenic	0.8244	pathogenic	-1.369	Destabilizing	0.979	D	0.823	deleterious	D	0.524958577	None	None	N
I/P	0.932	likely_pathogenic	0.897	pathogenic	-1.227	Destabilizing	0.984	D	0.833	deleterious	None	None	None	None	N
I/Q	0.9671	likely_pathogenic	0.9445	pathogenic	-1.412	Destabilizing	0.984	D	0.815	deleterious	None	None	None	None	N
I/R	0.9445	likely_pathogenic	0.9123	pathogenic	-0.887	Destabilizing	0.953	D	0.831	deleterious	None	None	None	None	N
I/S	0.9674	likely_pathogenic	0.9432	pathogenic	-2.132	Highly Destabilizing	0.815	D	0.813	deleterious	D	0.524198109	None	None	N
I/T	0.9487	likely_pathogenic	0.9111	pathogenic	-1.89	Destabilizing	0.684	D	0.795	deleterious	D	0.524198109	None	None	N
I/V	0.1912	likely_benign	0.1517	benign	-1.227	Destabilizing	0.003	N	0.227	neutral	N	0.518753735	None	None	N
I/W	0.9831	likely_pathogenic	0.9679	pathogenic	-1.398	Destabilizing	0.996	D	0.79	deleterious	None	None	None	None	N
I/Y	0.9442	likely_pathogenic	0.9057	pathogenic	-1.148	Destabilizing	0.953	D	0.84	deleterious	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.