TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21320	64183;64184;64185	chr2:178587253;178587252;178587251	chr2:179451980;179451979;179451978
N2AB	19679	59260;59261;59262	chr2:178587253;178587252;178587251	chr2:179451980;179451979;179451978
N2A	18752	56479;56480;56481	chr2:178587253;178587252;178587251	chr2:179451980;179451979;179451978
N2B	12255	36988;36989;36990	chr2:178587253;178587252;178587251	chr2:179451980;179451979;179451978
Novex-1	12380	37363;37364;37365	chr2:178587253;178587252;178587251	chr2:179451980;179451979;179451978
Novex-2	12447	37564;37565;37566	chr2:178587253;178587252;178587251	chr2:179451980;179451979;179451978
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-42
• Domain position: 55
• Structural Position: 77
• Q(SASA): 0.1043
• 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/F	rs1391961296	None	0.934	N	0.611	0.254	0.574945690627	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/F	rs1391961296	None	0.934	N	0.611	0.254	0.574945690627	gnomAD-4.0.0	6.57869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47119E-05	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
V/A	0.2557	likely_benign	0.2769	benign	-1.752	Destabilizing	0.625	D	0.409	neutral	N	0.507472374	None	None	N
V/C	0.6271	likely_pathogenic	0.6501	pathogenic	-1.039	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
V/D	0.7765	likely_pathogenic	0.782	pathogenic	-2.641	Highly Destabilizing	0.934	D	0.631	neutral	N	0.473290888	None	None	N
V/E	0.6275	likely_pathogenic	0.6511	pathogenic	-2.37	Highly Destabilizing	0.728	D	0.569	neutral	None	None	None	None	N
V/F	0.3629	ambiguous	0.4014	ambiguous	-1.008	Destabilizing	0.934	D	0.611	neutral	N	0.479913933	None	None	N
V/G	0.3379	likely_benign	0.3392	benign	-2.309	Highly Destabilizing	0.891	D	0.609	neutral	N	0.492425564	None	None	N
V/H	0.8315	likely_pathogenic	0.852	pathogenic	-2.322	Highly Destabilizing	0.993	D	0.574	neutral	None	None	None	None	N
V/I	0.0811	likely_benign	0.0927	benign	-0.17	Destabilizing	0.454	N	0.369	neutral	N	0.465204464	None	None	N
V/K	0.7977	likely_pathogenic	0.7971	pathogenic	-1.387	Destabilizing	0.728	D	0.571	neutral	None	None	None	None	N
V/L	0.2014	likely_benign	0.2362	benign	-0.17	Destabilizing	0.002	N	0.135	neutral	N	0.467935338	None	None	N
V/M	0.1758	likely_benign	0.2051	benign	-0.239	Destabilizing	0.949	D	0.593	neutral	None	None	None	None	N
V/N	0.4412	ambiguous	0.5068	ambiguous	-1.882	Destabilizing	0.974	D	0.623	neutral	None	None	None	None	N
V/P	0.8869	likely_pathogenic	0.868	pathogenic	-0.673	Destabilizing	0.991	D	0.602	neutral	None	None	None	None	N
V/Q	0.6111	likely_pathogenic	0.634	pathogenic	-1.614	Destabilizing	0.172	N	0.5	neutral	None	None	None	None	N
V/R	0.7636	likely_pathogenic	0.7549	pathogenic	-1.443	Destabilizing	0.949	D	0.633	neutral	None	None	None	None	N
V/S	0.3473	ambiguous	0.3839	ambiguous	-2.391	Highly Destabilizing	0.842	D	0.572	neutral	None	None	None	None	N
V/T	0.2761	likely_benign	0.3109	benign	-1.977	Destabilizing	0.915	D	0.491	neutral	None	None	None	None	N
V/W	0.9241	likely_pathogenic	0.9339	pathogenic	-1.666	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	N
V/Y	0.761	likely_pathogenic	0.7846	pathogenic	-1.191	Destabilizing	0.974	D	0.603	neutral	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.