TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21073	63442;63443;63444	chr2:178588190;178588189;178588188	chr2:179452917;179452916;179452915
N2AB	19432	58519;58520;58521	chr2:178588190;178588189;178588188	chr2:179452917;179452916;179452915
N2A	18505	55738;55739;55740	chr2:178588190;178588189;178588188	chr2:179452917;179452916;179452915
N2B	12008	36247;36248;36249	chr2:178588190;178588189;178588188	chr2:179452917;179452916;179452915
Novex-1	12133	36622;36623;36624	chr2:178588190;178588189;178588188	chr2:179452917;179452916;179452915
Novex-2	12200	36823;36824;36825	chr2:178588190;178588189;178588188	chr2:179452917;179452916;179452915
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-41
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3976
• 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
V/M	rs777982485	-0.568	1.0	N	0.785	0.468	0.563246863647	gnomAD-2.1.1	8.48E-06	None	None	None	None	N	None	0	3.02E-05	None	0	0	None	3.67E-05	None	0	0	0
V/M	rs777982485	-0.568	1.0	N	0.785	0.468	0.563246863647	gnomAD-4.0.0	2.09176E-06	None	None	None	None	N	None	0	2.3084E-05	None	0	0	None	0	0	0	1.20607E-05	1.69153E-05

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
V/A	0.3024	likely_benign	0.291	benign	-1.442	Destabilizing	0.999	D	0.655	neutral	N	0.467774387	None	None	N
V/C	0.8554	likely_pathogenic	0.8308	pathogenic	-1.245	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/D	0.8763	likely_pathogenic	0.8722	pathogenic	-0.989	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
V/E	0.7655	likely_pathogenic	0.7664	pathogenic	-0.874	Destabilizing	1.0	D	0.875	deleterious	D	0.524158429	None	None	N
V/F	0.5109	ambiguous	0.5089	ambiguous	-0.809	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/G	0.5753	likely_pathogenic	0.5776	pathogenic	-1.859	Destabilizing	1.0	D	0.855	deleterious	N	0.505040216	None	None	N
V/H	0.9259	likely_pathogenic	0.917	pathogenic	-1.188	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/I	0.0868	likely_benign	0.0836	benign	-0.354	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	N
V/K	0.8332	likely_pathogenic	0.8209	pathogenic	-1.222	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/L	0.4059	ambiguous	0.3718	ambiguous	-0.354	Destabilizing	0.997	D	0.649	neutral	N	0.516444148	None	None	N
V/M	0.3211	likely_benign	0.3024	benign	-0.497	Destabilizing	1.0	D	0.785	deleterious	N	0.511788166	None	None	N
V/N	0.7854	likely_pathogenic	0.7712	pathogenic	-1.344	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/P	0.622	likely_pathogenic	0.5893	pathogenic	-0.683	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/Q	0.8021	likely_pathogenic	0.7891	pathogenic	-1.287	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/R	0.8035	likely_pathogenic	0.7937	pathogenic	-0.913	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/S	0.6392	likely_pathogenic	0.6038	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/T	0.4468	ambiguous	0.4104	ambiguous	-1.743	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
V/W	0.9576	likely_pathogenic	0.9554	pathogenic	-1.047	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/Y	0.8746	likely_pathogenic	0.8682	pathogenic	-0.71	Destabilizing	1.0	D	0.875	deleterious	None	None	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.