TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8012	24259;24260;24261	chr2:178719356;178719355;178719354	chr2:179584083;179584082;179584081
N2AB	7695	23308;23309;23310	chr2:178719356;178719355;178719354	chr2:179584083;179584082;179584081
N2A	6768	20527;20528;20529	chr2:178719356;178719355;178719354	chr2:179584083;179584082;179584081
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-65
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.5578
• 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
A/P	rs749655622	-0.364	None	N	0.113	0.289	0.201204373187	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
A/P	rs749655622	-0.364	None	N	0.113	0.289	0.201204373187	gnomAD-4.0.0	1.59122E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85834E-06	0	0
A/T	rs749655622	None	0.042	N	0.371	0.127	0.299086750705	gnomAD-4.0.0	1.59122E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02407E-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
A/C	0.4849	ambiguous	0.4681	ambiguous	-0.977	Destabilizing	0.667	D	0.458	neutral	None	None	None	None	I
A/D	0.1827	likely_benign	0.1771	benign	-0.607	Destabilizing	0.175	N	0.547	neutral	N	0.478358268	None	None	I
A/E	0.1602	likely_benign	0.1605	benign	-0.747	Destabilizing	0.124	N	0.484	neutral	None	None	None	None	I
A/F	0.222	likely_benign	0.2182	benign	-0.971	Destabilizing	0.497	N	0.515	neutral	None	None	None	None	I
A/G	0.1321	likely_benign	0.1354	benign	-0.362	Destabilizing	0.042	N	0.37	neutral	N	0.471392223	None	None	I
A/H	0.3166	likely_benign	0.3038	benign	-0.252	Destabilizing	0.883	D	0.472	neutral	None	None	None	None	I
A/I	0.1749	likely_benign	0.1727	benign	-0.518	Destabilizing	0.004	N	0.176	neutral	None	None	None	None	I
A/K	0.3035	likely_benign	0.304	benign	-0.683	Destabilizing	0.124	N	0.49	neutral	None	None	None	None	I
A/L	0.1115	likely_benign	0.1108	benign	-0.518	Destabilizing	None	N	0.127	neutral	None	None	None	None	I
A/M	0.1645	likely_benign	0.1682	benign	-0.727	Destabilizing	0.497	N	0.479	neutral	None	None	None	None	I
A/N	0.195	likely_benign	0.1898	benign	-0.426	Destabilizing	0.331	N	0.542	neutral	None	None	None	None	I
A/P	0.0836	likely_benign	0.0783	benign	-0.44	Destabilizing	None	N	0.113	neutral	N	0.277597418	None	None	I
A/Q	0.2269	likely_benign	0.2195	benign	-0.671	Destabilizing	0.497	N	0.511	neutral	None	None	None	None	I
A/R	0.2857	likely_benign	0.2782	benign	-0.233	Destabilizing	0.497	N	0.535	neutral	None	None	None	None	I
A/S	0.0754	likely_benign	0.0724	benign	-0.622	Destabilizing	0.001	N	0.123	neutral	N	0.429969675	None	None	I
A/T	0.0816	likely_benign	0.0814	benign	-0.689	Destabilizing	0.042	N	0.371	neutral	N	0.472952448	None	None	I
A/V	0.0973	likely_benign	0.0976	benign	-0.44	Destabilizing	0.042	N	0.329	neutral	N	0.479225059	None	None	I
A/W	0.5928	likely_pathogenic	0.5682	pathogenic	-1.051	Destabilizing	0.958	D	0.515	neutral	None	None	None	None	I
A/Y	0.3008	likely_benign	0.2911	benign	-0.764	Destabilizing	0.667	D	0.48	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.