TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19925	59998;59999;60000	chr2:178592131;178592130;178592129	chr2:179456858;179456857;179456856
N2AB	18284	55075;55076;55077	chr2:178592131;178592130;178592129	chr2:179456858;179456857;179456856
N2A	17357	52294;52295;52296	chr2:178592131;178592130;178592129	chr2:179456858;179456857;179456856
N2B	10860	32803;32804;32805	chr2:178592131;178592130;178592129	chr2:179456858;179456857;179456856
Novex-1	10985	33178;33179;33180	chr2:178592131;178592130;178592129	chr2:179456858;179456857;179456856
Novex-2	11052	33379;33380;33381	chr2:178592131;178592130;178592129	chr2:179456858;179456857;179456856
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-32
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.322
• 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
S/L	rs2050346497	None	None	N	0.153	0.233	0.521653710555	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
S/L	rs2050346497	None	None	N	0.153	0.233	0.521653710555	gnomAD-4.0.0	6.58354E-06	None	None	None	None	I	None	2.41721E-05	0	None	0	0	None	0	0	0	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
S/A	0.0759	likely_benign	0.0737	benign	-0.655	Destabilizing	0.021	N	0.163	neutral	N	0.435862992	None	None	I
S/C	0.082	likely_benign	0.0784	benign	-0.439	Destabilizing	0.94	D	0.321	neutral	None	None	None	None	I
S/D	0.3756	ambiguous	0.3737	ambiguous	0.198	Stabilizing	0.816	D	0.233	neutral	None	None	None	None	I
S/E	0.3342	likely_benign	0.3807	ambiguous	0.199	Stabilizing	0.593	D	0.219	neutral	None	None	None	None	I
S/F	0.1015	likely_benign	0.1038	benign	-0.808	Destabilizing	0.264	N	0.325	neutral	None	None	None	None	I
S/G	0.1173	likely_benign	0.0999	benign	-0.897	Destabilizing	0.375	N	0.233	neutral	None	None	None	None	I
S/H	0.1721	likely_benign	0.1943	benign	-1.205	Destabilizing	0.94	D	0.318	neutral	None	None	None	None	I
S/I	0.0699	likely_benign	0.0635	benign	-0.12	Destabilizing	None	N	0.154	neutral	None	None	None	None	I
S/K	0.3832	ambiguous	0.4553	ambiguous	-0.513	Destabilizing	0.593	D	0.223	neutral	None	None	None	None	I
S/L	0.0585	likely_benign	0.0599	benign	-0.12	Destabilizing	None	N	0.153	neutral	N	0.42408856	None	None	I
S/M	0.1019	likely_benign	0.0949	benign	-0.062	Destabilizing	0.716	D	0.382	neutral	None	None	None	None	I
S/N	0.0983	likely_benign	0.092	benign	-0.483	Destabilizing	0.816	D	0.267	neutral	None	None	None	None	I
S/P	0.6613	likely_pathogenic	0.7373	pathogenic	-0.264	Destabilizing	0.77	D	0.331	neutral	N	0.50280006	None	None	I
S/Q	0.2463	likely_benign	0.29	benign	-0.578	Destabilizing	0.94	D	0.34	neutral	None	None	None	None	I
S/R	0.3666	ambiguous	0.4225	ambiguous	-0.402	Destabilizing	0.593	D	0.385	neutral	None	None	None	None	I
S/T	0.0632	likely_benign	0.06	benign	-0.54	Destabilizing	0.183	N	0.256	neutral	N	0.382433939	None	None	I
S/V	0.08	likely_benign	0.0704	benign	-0.264	Destabilizing	None	N	0.153	neutral	None	None	None	None	I
S/W	0.2158	likely_benign	0.2333	benign	-0.795	Destabilizing	0.983	D	0.389	neutral	None	None	None	None	I
S/Y	0.104	likely_benign	0.111	benign	-0.518	Destabilizing	0.593	D	0.408	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.