TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32152	96679;96680;96681	chr2:178543519;178543518;178543517	chr2:179408246;179408245;179408244
N2AB	30511	91756;91757;91758	chr2:178543519;178543518;178543517	chr2:179408246;179408245;179408244
N2A	29584	88975;88976;88977	chr2:178543519;178543518;178543517	chr2:179408246;179408245;179408244
N2B	23087	69484;69485;69486	chr2:178543519;178543518;178543517	chr2:179408246;179408245;179408244
Novex-1	23212	69859;69860;69861	chr2:178543519;178543518;178543517	chr2:179408246;179408245;179408244
Novex-2	23279	70060;70061;70062	chr2:178543519;178543518;178543517	chr2:179408246;179408245;179408244
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-122
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.2546
• 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
F/L	None	None	0.349	N	0.451	0.344	0.417081434665	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
F/V	None	None	0.722	N	0.405	0.319	0.591140946133	gnomAD-4.0.0	1.59214E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85873E-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
F/A	0.9842	likely_pathogenic	0.9867	pathogenic	-2.424	Highly Destabilizing	0.775	D	0.465	neutral	None	None	None	None	I
F/C	0.9168	likely_pathogenic	0.9231	pathogenic	-1.082	Destabilizing	0.995	D	0.55	neutral	N	0.510283393	None	None	I
F/D	0.9935	likely_pathogenic	0.9949	pathogenic	-1.22	Destabilizing	0.987	D	0.585	neutral	None	None	None	None	I
F/E	0.9969	likely_pathogenic	0.9977	pathogenic	-1.143	Destabilizing	0.961	D	0.562	neutral	None	None	None	None	I
F/G	0.9896	likely_pathogenic	0.9911	pathogenic	-2.739	Highly Destabilizing	0.961	D	0.51	neutral	None	None	None	None	I
F/H	0.9099	likely_pathogenic	0.9311	pathogenic	-0.839	Destabilizing	0.923	D	0.484	neutral	None	None	None	None	I
F/I	0.9569	likely_pathogenic	0.9601	pathogenic	-1.469	Destabilizing	0.722	D	0.431	neutral	N	0.480307203	None	None	I
F/K	0.9973	likely_pathogenic	0.998	pathogenic	-1.076	Destabilizing	0.923	D	0.569	neutral	None	None	None	None	I
F/L	0.9932	likely_pathogenic	0.9931	pathogenic	-1.469	Destabilizing	0.349	N	0.451	neutral	N	0.471802363	None	None	I
F/M	0.9682	likely_pathogenic	0.9694	pathogenic	-1.094	Destabilizing	0.987	D	0.453	neutral	None	None	None	None	I
F/N	0.974	likely_pathogenic	0.9805	pathogenic	-1.071	Destabilizing	0.961	D	0.585	neutral	None	None	None	None	I
F/P	0.996	likely_pathogenic	0.9972	pathogenic	-1.783	Destabilizing	0.987	D	0.588	neutral	None	None	None	None	I
F/Q	0.9916	likely_pathogenic	0.9936	pathogenic	-1.253	Destabilizing	0.961	D	0.587	neutral	None	None	None	None	I
F/R	0.9917	likely_pathogenic	0.9935	pathogenic	-0.307	Destabilizing	0.961	D	0.591	neutral	None	None	None	None	I
F/S	0.9575	likely_pathogenic	0.9645	pathogenic	-1.886	Destabilizing	0.901	D	0.467	neutral	N	0.471108929	None	None	I
F/T	0.9871	likely_pathogenic	0.9897	pathogenic	-1.727	Destabilizing	0.961	D	0.484	neutral	None	None	None	None	I
F/V	0.9411	likely_pathogenic	0.948	pathogenic	-1.783	Destabilizing	0.722	D	0.405	neutral	N	0.491004199	None	None	I
F/W	0.3142	likely_benign	0.3433	ambiguous	-0.488	Destabilizing	0.961	D	0.461	neutral	None	None	None	None	I
F/Y	0.128	likely_benign	0.1393	benign	-0.69	Destabilizing	0.001	N	0.114	neutral	N	0.386455679	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.