TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26513	79762;79763;79764	chr2:178566595;178566594;178566593	chr2:179431322;179431321;179431320
N2AB	24872	74839;74840;74841	chr2:178566595;178566594;178566593	chr2:179431322;179431321;179431320
N2A	23945	72058;72059;72060	chr2:178566595;178566594;178566593	chr2:179431322;179431321;179431320
N2B	17448	52567;52568;52569	chr2:178566595;178566594;178566593	chr2:179431322;179431321;179431320
Novex-1	17573	52942;52943;52944	chr2:178566595;178566594;178566593	chr2:179431322;179431321;179431320
Novex-2	17640	53143;53144;53145	chr2:178566595;178566594;178566593	chr2:179431322;179431321;179431320
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-81
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4843
• 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
Y/C	rs1575685631	None	1.0	N	0.679	0.505	0.372993862945	gnomAD-4.0.0	4.793E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29672E-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
Y/A	0.8392	likely_pathogenic	0.9004	pathogenic	-0.977	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
Y/C	0.4325	ambiguous	0.5515	ambiguous	-0.041	Destabilizing	1.0	D	0.679	prob.neutral	N	0.484036584	None	None	I
Y/D	0.7363	likely_pathogenic	0.8312	pathogenic	0.864	Stabilizing	1.0	D	0.7	prob.neutral	N	0.444025824	None	None	I
Y/E	0.9391	likely_pathogenic	0.965	pathogenic	0.857	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
Y/F	0.2164	likely_benign	0.27	benign	-0.483	Destabilizing	0.999	D	0.496	neutral	N	0.501978049	None	None	I
Y/G	0.7488	likely_pathogenic	0.8287	pathogenic	-1.18	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
Y/H	0.5731	likely_pathogenic	0.7408	pathogenic	0.042	Stabilizing	1.0	D	0.663	neutral	N	0.492358488	None	None	I
Y/I	0.8735	likely_pathogenic	0.9179	pathogenic	-0.451	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
Y/K	0.9251	likely_pathogenic	0.96	pathogenic	0.004	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
Y/L	0.7781	likely_pathogenic	0.8336	pathogenic	-0.451	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	I
Y/M	0.8658	likely_pathogenic	0.9199	pathogenic	-0.212	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
Y/N	0.5167	ambiguous	0.6934	pathogenic	-0.195	Destabilizing	1.0	D	0.696	prob.neutral	N	0.472540576	None	None	I
Y/P	0.9785	likely_pathogenic	0.9858	pathogenic	-0.608	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
Y/Q	0.8884	likely_pathogenic	0.9468	pathogenic	-0.157	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
Y/R	0.815	likely_pathogenic	0.8916	pathogenic	0.329	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
Y/S	0.481	ambiguous	0.6408	pathogenic	-0.685	Destabilizing	1.0	D	0.69	prob.neutral	N	0.492587775	None	None	I
Y/T	0.7638	likely_pathogenic	0.8714	pathogenic	-0.604	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
Y/V	0.7801	likely_pathogenic	0.8485	pathogenic	-0.608	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
Y/W	0.6555	likely_pathogenic	0.7087	pathogenic	-0.513	Destabilizing	1.0	D	0.645	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.