TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8559	25900;25901;25902	chr2:178715739;178715738;178715737	chr2:179580466;179580465;179580464
N2AB	8242	24949;24950;24951	chr2:178715739;178715738;178715737	chr2:179580466;179580465;179580464
N2A	7315	22168;22169;22170	chr2:178715739;178715738;178715737	chr2:179580466;179580465;179580464
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-71
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.8506
• 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
R/K	rs745818225	0.088	None	N	0.193	0.261	0.382925413656	gnomAD-2.1.1	4.72E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.09E-05	0
R/K	rs745818225	0.088	None	N	0.193	0.261	0.382925413656	gnomAD-4.0.0	2.08309E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.72746E-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
R/A	0.3585	ambiguous	0.3322	benign	-1.134	Destabilizing	0.767	D	0.5	neutral	None	None	None	None	I
R/C	0.1868	likely_benign	0.1872	benign	-1.085	Destabilizing	0.998	D	0.481	neutral	None	None	None	None	I
R/D	0.6292	likely_pathogenic	0.5924	pathogenic	-0.082	Destabilizing	0.888	D	0.503	neutral	None	None	None	None	I
R/E	0.319	likely_benign	0.293	benign	0.09	Stabilizing	0.331	N	0.485	neutral	None	None	None	None	I
R/F	0.4932	ambiguous	0.4641	ambiguous	-0.776	Destabilizing	0.986	D	0.481	neutral	None	None	None	None	I
R/G	0.2498	likely_benign	0.2369	benign	-1.478	Destabilizing	0.857	D	0.536	neutral	D	0.533846191	None	None	I
R/H	0.0959	likely_benign	0.0936	benign	-1.67	Destabilizing	0.986	D	0.448	neutral	None	None	None	None	I
R/I	0.2242	likely_benign	0.2104	benign	-0.186	Destabilizing	0.947	D	0.495	neutral	N	0.467119767	None	None	I
R/K	0.0881	likely_benign	0.082	benign	-0.793	Destabilizing	None	N	0.193	neutral	N	0.449536871	None	None	I
R/L	0.2308	likely_benign	0.219	benign	-0.186	Destabilizing	0.768	D	0.536	neutral	None	None	None	None	I
R/M	0.2465	likely_benign	0.2282	benign	-0.623	Destabilizing	0.986	D	0.473	neutral	None	None	None	None	I
R/N	0.5107	ambiguous	0.4756	ambiguous	-0.51	Destabilizing	0.888	D	0.488	neutral	None	None	None	None	I
R/P	0.7932	likely_pathogenic	0.7791	pathogenic	-0.483	Destabilizing	0.983	D	0.501	neutral	None	None	None	None	I
R/Q	0.0955	likely_benign	0.0916	benign	-0.569	Destabilizing	0.855	D	0.521	neutral	None	None	None	None	I
R/S	0.4302	ambiguous	0.3997	ambiguous	-1.394	Destabilizing	0.857	D	0.529	neutral	N	0.520474249	None	None	I
R/T	0.2222	likely_benign	0.2027	benign	-1.005	Destabilizing	0.857	D	0.522	neutral	N	0.45746292	None	None	I
R/V	0.2808	likely_benign	0.2656	benign	-0.483	Destabilizing	0.944	D	0.482	neutral	None	None	None	None	I
R/W	0.1767	likely_benign	0.1743	benign	-0.358	Destabilizing	0.999	D	0.536	neutral	None	None	None	None	I
R/Y	0.3495	ambiguous	0.3352	benign	-0.122	Destabilizing	0.986	D	0.491	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.