TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25628	77107;77108;77109	chr2:178569250;178569249;178569248	chr2:179433977;179433976;179433975
N2AB	23987	72184;72185;72186	chr2:178569250;178569249;178569248	chr2:179433977;179433976;179433975
N2A	23060	69403;69404;69405	chr2:178569250;178569249;178569248	chr2:179433977;179433976;179433975
N2B	16563	49912;49913;49914	chr2:178569250;178569249;178569248	chr2:179433977;179433976;179433975
Novex-1	16688	50287;50288;50289	chr2:178569250;178569249;178569248	chr2:179433977;179433976;179433975
Novex-2	16755	50488;50489;50490	chr2:178569250;178569249;178569248	chr2:179433977;179433976;179433975
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-74
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2374
• 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
D/V	None	None	1.0	D	0.683	0.611	0.798450862424	gnomAD-4.0.0	1.61563E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.90102E-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
D/A	0.9222	likely_pathogenic	0.9358	pathogenic	-0.542	Destabilizing	1.0	D	0.701	prob.neutral	N	0.510339226	None	None	I
D/C	0.9832	likely_pathogenic	0.9867	pathogenic	-0.013	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	I
D/E	0.8339	likely_pathogenic	0.8429	pathogenic	-0.632	Destabilizing	0.994	D	0.438	neutral	N	0.504058576	None	None	I
D/F	0.9893	likely_pathogenic	0.9906	pathogenic	-0.586	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	I
D/G	0.9062	likely_pathogenic	0.9236	pathogenic	-0.812	Destabilizing	1.0	D	0.665	neutral	D	0.524697726	None	None	I
D/H	0.9536	likely_pathogenic	0.9628	pathogenic	-0.892	Destabilizing	1.0	D	0.63	neutral	D	0.523937257	None	None	I
D/I	0.9809	likely_pathogenic	0.9853	pathogenic	0.146	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	I
D/K	0.9888	likely_pathogenic	0.9896	pathogenic	-0.012	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/L	0.9673	likely_pathogenic	0.9736	pathogenic	0.146	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
D/M	0.9923	likely_pathogenic	0.9935	pathogenic	0.618	Stabilizing	1.0	D	0.624	neutral	None	None	None	None	I
D/N	0.4896	ambiguous	0.5495	ambiguous	-0.347	Destabilizing	1.0	D	0.669	neutral	N	0.474219621	None	None	I
D/P	0.9881	likely_pathogenic	0.9915	pathogenic	-0.06	Destabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	I
D/Q	0.9751	likely_pathogenic	0.9786	pathogenic	-0.282	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
D/R	0.9847	likely_pathogenic	0.9867	pathogenic	-0.041	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
D/S	0.7786	likely_pathogenic	0.8129	pathogenic	-0.519	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
D/T	0.9239	likely_pathogenic	0.9313	pathogenic	-0.296	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
D/V	0.9486	likely_pathogenic	0.9571	pathogenic	-0.06	Destabilizing	1.0	D	0.683	prob.neutral	D	0.530013644	None	None	I
D/W	0.9971	likely_pathogenic	0.9975	pathogenic	-0.479	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	I
D/Y	0.919	likely_pathogenic	0.9296	pathogenic	-0.351	Destabilizing	1.0	D	0.615	neutral	D	0.554158286	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.