TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18429	55510;55511;55512	chr2:178601899;178601898;178601897	chr2:179466626;179466625;179466624
N2AB	16788	50587;50588;50589	chr2:178601899;178601898;178601897	chr2:179466626;179466625;179466624
N2A	15861	47806;47807;47808	chr2:178601899;178601898;178601897	chr2:179466626;179466625;179466624
N2B	9364	28315;28316;28317	chr2:178601899;178601898;178601897	chr2:179466626;179466625;179466624
Novex-1	9489	28690;28691;28692	chr2:178601899;178601898;178601897	chr2:179466626;179466625;179466624
Novex-2	9556	28891;28892;28893	chr2:178601899;178601898;178601897	chr2:179466626;179466625;179466624
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-115
• Domain position: 48
• Structural Position: 68
• Q(SASA): 0.1988
• 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/M	None	None	0.317	N	0.668	0.043	0.247322355667	gnomAD-4.0.0	2.05506E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70002E-06	0	0
I/T	None	None	0.002	N	0.415	0.155	0.454331543959	gnomAD-4.0.0	1.5954E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43885E-05	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	0.744	likely_pathogenic	0.7566	pathogenic	-3.148	Highly Destabilizing	0.035	N	0.574	neutral	None	None	None	None	N
I/C	0.8074	likely_pathogenic	0.809	pathogenic	-2.585	Highly Destabilizing	0.824	D	0.625	neutral	None	None	None	None	N
I/D	0.9734	likely_pathogenic	0.982	pathogenic	-3.814	Highly Destabilizing	0.555	D	0.645	neutral	None	None	None	None	N
I/E	0.9566	likely_pathogenic	0.9688	pathogenic	-3.506	Highly Destabilizing	0.555	D	0.646	neutral	None	None	None	None	N
I/F	0.2351	likely_benign	0.2512	benign	-1.794	Destabilizing	0.38	N	0.639	neutral	None	None	None	None	N
I/G	0.9216	likely_pathogenic	0.9311	pathogenic	-3.749	Highly Destabilizing	0.262	N	0.63	neutral	None	None	None	None	N
I/H	0.9185	likely_pathogenic	0.9365	pathogenic	-3.289	Highly Destabilizing	0.935	D	0.657	neutral	None	None	None	None	N
I/K	0.8952	likely_pathogenic	0.9273	pathogenic	-2.443	Highly Destabilizing	0.484	N	0.647	neutral	N	0.483259002	None	None	N
I/L	0.0971	likely_benign	0.0966	benign	-1.335	Destabilizing	0.012	N	0.449	neutral	N	0.341613532	None	None	N
I/M	0.1592	likely_benign	0.1613	benign	-1.601	Destabilizing	0.317	N	0.668	neutral	N	0.431600818	None	None	N
I/N	0.8113	likely_pathogenic	0.8612	pathogenic	-3.113	Highly Destabilizing	0.555	D	0.659	neutral	None	None	None	None	N
I/P	0.9321	likely_pathogenic	0.9553	pathogenic	-1.931	Destabilizing	0.555	D	0.655	neutral	None	None	None	None	N
I/Q	0.9116	likely_pathogenic	0.9325	pathogenic	-2.795	Highly Destabilizing	0.791	D	0.669	neutral	None	None	None	None	N
I/R	0.8652	likely_pathogenic	0.9078	pathogenic	-2.334	Highly Destabilizing	0.484	N	0.658	neutral	N	0.483432361	None	None	N
I/S	0.7917	likely_pathogenic	0.8219	pathogenic	-3.716	Highly Destabilizing	0.081	N	0.592	neutral	None	None	None	None	N
I/T	0.6473	likely_pathogenic	0.6695	pathogenic	-3.251	Highly Destabilizing	0.002	N	0.415	neutral	N	0.445124689	None	None	N
I/V	0.0907	likely_benign	0.0907	benign	-1.931	Destabilizing	None	N	0.272	neutral	N	0.438678719	None	None	N
I/W	0.9173	likely_pathogenic	0.9313	pathogenic	-2.227	Highly Destabilizing	0.935	D	0.682	prob.neutral	None	None	None	None	N
I/Y	0.758	likely_pathogenic	0.7954	pathogenic	-2.093	Highly Destabilizing	0.555	D	0.637	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.