TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5179	15760;15761;15762	chr2:178733854;178733853;178733852	chr2:179598581;179598580;179598579
N2AB	4862	14809;14810;14811	chr2:178733854;178733853;178733852	chr2:179598581;179598580;179598579
N2A	3935	12028;12029;12030	chr2:178733854;178733853;178733852	chr2:179598581;179598580;179598579
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-35
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1675
• 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
A/T	rs536853382	None	0.034	N	0.369	0.25	0.285316908763	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-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
A/C	0.411	ambiguous	0.4227	ambiguous	-0.838	Destabilizing	0.996	D	0.571	neutral	None	None	None	None	I
A/D	0.6172	likely_pathogenic	0.6775	pathogenic	-1.313	Destabilizing	0.923	D	0.62	neutral	None	None	None	None	I
A/E	0.4904	ambiguous	0.5377	ambiguous	-1.256	Destabilizing	0.901	D	0.627	neutral	D	0.581302887	None	None	I
A/F	0.357	ambiguous	0.3846	ambiguous	-0.683	Destabilizing	0.923	D	0.626	neutral	None	None	None	None	I
A/G	0.1816	likely_benign	0.2076	benign	-1.194	Destabilizing	0.565	D	0.517	neutral	D	0.564029223	None	None	I
A/H	0.6537	likely_pathogenic	0.6943	pathogenic	-1.421	Destabilizing	0.996	D	0.603	neutral	None	None	None	None	I
A/I	0.1917	likely_benign	0.2004	benign	-0.028	Destabilizing	0.372	N	0.602	neutral	None	None	None	None	I
A/K	0.6949	likely_pathogenic	0.7442	pathogenic	-1.337	Destabilizing	0.923	D	0.635	neutral	None	None	None	None	I
A/L	0.2005	likely_benign	0.2191	benign	-0.028	Destabilizing	0.633	D	0.493	neutral	None	None	None	None	I
A/M	0.2607	likely_benign	0.2787	benign	-0.08	Destabilizing	0.979	D	0.608	neutral	None	None	None	None	I
A/N	0.5097	ambiguous	0.5618	ambiguous	-1.211	Destabilizing	0.923	D	0.633	neutral	None	None	None	None	I
A/P	0.7441	likely_pathogenic	0.7858	pathogenic	-0.258	Destabilizing	0.949	D	0.642	neutral	D	0.62971059	None	None	I
A/Q	0.5365	ambiguous	0.5785	pathogenic	-1.221	Destabilizing	0.961	D	0.619	neutral	None	None	None	None	I
A/R	0.6252	likely_pathogenic	0.6612	pathogenic	-1.112	Destabilizing	0.923	D	0.645	neutral	None	None	None	None	I
A/S	0.1173	likely_benign	0.1249	benign	-1.601	Destabilizing	0.075	N	0.345	neutral	N	0.511034339	None	None	I
A/T	0.0902	likely_benign	0.0921	benign	-1.436	Destabilizing	0.034	N	0.369	neutral	N	0.47861351	None	None	I
A/V	0.0932	likely_benign	0.0916	benign	-0.258	Destabilizing	0.008	N	0.235	neutral	N	0.415607286	None	None	I
A/W	0.8451	likely_pathogenic	0.8686	pathogenic	-1.205	Destabilizing	0.996	D	0.63	neutral	None	None	None	None	I
A/Y	0.571	likely_pathogenic	0.6217	pathogenic	-0.724	Destabilizing	0.961	D	0.633	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.