TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5230	15913;15914;15915	chr2:178733701;178733700;178733699	chr2:179598428;179598427;179598426
N2AB	4913	14962;14963;14964	chr2:178733701;178733700;178733699	chr2:179598428;179598427;179598426
N2A	3986	12181;12182;12183	chr2:178733701;178733700;178733699	chr2:179598428;179598427;179598426
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-35
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0984
• 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/I	rs369294144	-0.849	0.117	N	0.337	0.157	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/I	rs369294144	-0.849	0.117	N	0.337	0.157	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs369294144	-0.849	0.117	N	0.337	0.157	None	gnomAD-4.0.0	2.47869E-06	None	None	None	None	N	None	2.66944E-05	0	None	0	0	None	0	0	0	0	3.20246E-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	0.2309	likely_benign	0.3019	benign	-2.202	Highly Destabilizing	0.977	D	0.517	neutral	N	0.48065576	None	None	N
V/C	0.8008	likely_pathogenic	0.8281	pathogenic	-2.197	Highly Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
V/D	0.8874	likely_pathogenic	0.9518	pathogenic	-2.911	Highly Destabilizing	0.999	D	0.776	deleterious	D	0.73581048	None	None	N
V/E	0.8433	likely_pathogenic	0.9184	pathogenic	-2.75	Highly Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
V/F	0.5281	ambiguous	0.666	pathogenic	-1.465	Destabilizing	0.993	D	0.775	deleterious	D	0.631228988	None	None	N
V/G	0.4421	ambiguous	0.5623	ambiguous	-2.681	Highly Destabilizing	0.999	D	0.749	deleterious	D	0.659526353	None	None	N
V/H	0.945	likely_pathogenic	0.9758	pathogenic	-2.286	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
V/I	0.0797	likely_benign	0.0895	benign	-0.888	Destabilizing	0.117	N	0.337	neutral	N	0.515955965	None	None	N
V/K	0.9017	likely_pathogenic	0.9541	pathogenic	-1.881	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
V/L	0.3072	likely_benign	0.3853	ambiguous	-0.888	Destabilizing	0.898	D	0.503	neutral	D	0.546080145	None	None	N
V/M	0.2492	likely_benign	0.3441	ambiguous	-1.089	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	N
V/N	0.6832	likely_pathogenic	0.8232	pathogenic	-2.148	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
V/P	0.7874	likely_pathogenic	0.8934	pathogenic	-1.298	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
V/Q	0.8513	likely_pathogenic	0.9214	pathogenic	-2.107	Highly Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
V/R	0.8707	likely_pathogenic	0.9285	pathogenic	-1.564	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
V/S	0.4018	ambiguous	0.5259	ambiguous	-2.763	Highly Destabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	N
V/T	0.2588	likely_benign	0.3402	ambiguous	-2.465	Highly Destabilizing	0.983	D	0.663	neutral	None	None	None	None	N
V/W	0.9783	likely_pathogenic	0.9913	pathogenic	-1.872	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
V/Y	0.9163	likely_pathogenic	0.958	pathogenic	-1.549	Destabilizing	0.999	D	0.789	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.