TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8379	25360;25361;25362	chr2:178717739;178717738;178717737	chr2:179582466;179582465;179582464
N2AB	8062	24409;24410;24411	chr2:178717739;178717738;178717737	chr2:179582466;179582465;179582464
N2A	7135	21628;21629;21630	chr2:178717739;178717738;178717737	chr2:179582466;179582465;179582464
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-69
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1146
• 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
F/S	rs761873646	-3.296	0.997	D	0.639	0.79	0.85668431153	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	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
F/A	0.9782	likely_pathogenic	0.9865	pathogenic	-2.104	Highly Destabilizing	0.989	D	0.744	deleterious	None	None	None	None	N
F/C	0.9636	likely_pathogenic	0.9801	pathogenic	-1.188	Destabilizing	0.7	D	0.677	prob.neutral	D	0.61520018	None	None	N
F/D	0.9991	likely_pathogenic	0.9996	pathogenic	-3.188	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
F/E	0.9984	likely_pathogenic	0.9991	pathogenic	-2.941	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
F/G	0.9937	likely_pathogenic	0.9966	pathogenic	-2.555	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
F/H	0.9926	likely_pathogenic	0.9959	pathogenic	-2.003	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
F/I	0.6838	likely_pathogenic	0.7353	pathogenic	-0.617	Destabilizing	0.985	D	0.651	neutral	D	0.538340439	None	None	N
F/K	0.9982	likely_pathogenic	0.999	pathogenic	-1.949	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
F/L	0.8785	likely_pathogenic	0.9111	pathogenic	-0.617	Destabilizing	0.149	N	0.294	neutral	N	0.454326615	None	None	N
F/M	0.7747	likely_pathogenic	0.8182	pathogenic	-0.475	Destabilizing	0.983	D	0.657	neutral	None	None	None	None	N
F/N	0.997	likely_pathogenic	0.9985	pathogenic	-2.703	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
F/P	0.9996	likely_pathogenic	0.9998	pathogenic	-1.128	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
F/Q	0.9965	likely_pathogenic	0.9982	pathogenic	-2.389	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
F/R	0.9947	likely_pathogenic	0.9972	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
F/S	0.9892	likely_pathogenic	0.9942	pathogenic	-3.026	Highly Destabilizing	0.997	D	0.639	neutral	D	0.615200181	None	None	N
F/T	0.9878	likely_pathogenic	0.9926	pathogenic	-2.647	Highly Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
F/V	0.7267	likely_pathogenic	0.7783	pathogenic	-1.128	Destabilizing	0.98	D	0.683	prob.neutral	N	0.51397998	None	None	N
F/W	0.8925	likely_pathogenic	0.9216	pathogenic	-0.234	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
F/Y	0.7202	likely_pathogenic	0.7731	pathogenic	-0.606	Destabilizing	0.997	D	0.616	neutral	D	0.58272749	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.