TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26479	79660;79661;79662	chr2:178566697;178566696;178566695	chr2:179431424;179431423;179431422
N2AB	24838	74737;74738;74739	chr2:178566697;178566696;178566695	chr2:179431424;179431423;179431422
N2A	23911	71956;71957;71958	chr2:178566697;178566696;178566695	chr2:179431424;179431423;179431422
N2B	17414	52465;52466;52467	chr2:178566697;178566696;178566695	chr2:179431424;179431423;179431422
Novex-1	17539	52840;52841;52842	chr2:178566697;178566696;178566695	chr2:179431424;179431423;179431422
Novex-2	17606	53041;53042;53043	chr2:178566697;178566696;178566695	chr2:179431424;179431423;179431422
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: Fn3-80
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.6739
• 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	None	None	0.993	N	0.508	0.263	0.601923037437	gnomAD-4.0.0	1.59216E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85896E-06	0	0
Y/F	rs747150576	-0.485	0.002	N	0.187	0.163	0.294918367191	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
Y/F	rs747150576	-0.485	0.002	N	0.187	0.163	0.294918367191	gnomAD-4.0.0	1.59216E-06	None	None	None	None	I	None	5.65803E-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
Y/A	0.4306	ambiguous	0.4037	ambiguous	-2.367	Highly Destabilizing	0.834	D	0.545	neutral	None	None	None	None	I
Y/C	0.1074	likely_benign	0.081	benign	-1.356	Destabilizing	0.993	D	0.508	neutral	N	0.485163718	None	None	I
Y/D	0.6589	likely_pathogenic	0.5876	pathogenic	-1.756	Destabilizing	0.976	D	0.561	neutral	N	0.485163718	None	None	I
Y/E	0.7368	likely_pathogenic	0.6888	pathogenic	-1.612	Destabilizing	0.982	D	0.578	neutral	None	None	None	None	I
Y/F	0.0867	likely_benign	0.0743	benign	-0.91	Destabilizing	0.002	N	0.187	neutral	N	0.503911994	None	None	I
Y/G	0.5393	ambiguous	0.4954	ambiguous	-2.718	Highly Destabilizing	0.834	D	0.611	neutral	None	None	None	None	I
Y/H	0.2049	likely_benign	0.1623	benign	-1.111	Destabilizing	0.976	D	0.547	neutral	N	0.473553923	None	None	I
Y/I	0.3336	likely_benign	0.2835	benign	-1.259	Destabilizing	0.553	D	0.527	neutral	None	None	None	None	I
Y/K	0.6563	likely_pathogenic	0.611	pathogenic	-1.736	Destabilizing	0.982	D	0.592	neutral	None	None	None	None	I
Y/L	0.3868	ambiguous	0.3594	ambiguous	-1.259	Destabilizing	0.003	N	0.186	neutral	None	None	None	None	I
Y/M	0.5092	ambiguous	0.4706	ambiguous	-1.017	Destabilizing	0.897	D	0.567	neutral	None	None	None	None	I
Y/N	0.3836	ambiguous	0.3022	benign	-2.354	Highly Destabilizing	0.976	D	0.583	neutral	N	0.484910228	None	None	I
Y/P	0.9444	likely_pathogenic	0.9371	pathogenic	-1.631	Destabilizing	0.982	D	0.529	neutral	None	None	None	None	I
Y/Q	0.4378	ambiguous	0.3746	ambiguous	-2.149	Highly Destabilizing	0.982	D	0.601	neutral	None	None	None	None	I
Y/R	0.466	ambiguous	0.406	ambiguous	-1.453	Destabilizing	0.982	D	0.575	neutral	None	None	None	None	I
Y/S	0.251	likely_benign	0.2205	benign	-2.789	Highly Destabilizing	0.791	D	0.605	neutral	N	0.48389627	None	None	I
Y/T	0.3635	ambiguous	0.3243	benign	-2.536	Highly Destabilizing	0.834	D	0.589	neutral	None	None	None	None	I
Y/V	0.2388	likely_benign	0.2133	benign	-1.631	Destabilizing	0.338	N	0.511	neutral	None	None	None	None	I
Y/W	0.4274	ambiguous	0.3439	ambiguous	-0.42	Destabilizing	0.018	N	0.241	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.