TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4748	14467;14468;14469	chr2:178738211;178738210;178738209	chr2:179602938;179602937;179602936
N2AB	4431	13516;13517;13518	chr2:178738211;178738210;178738209	chr2:179602938;179602937;179602936
N2A	3504	10735;10736;10737	chr2:178738211;178738210;178738209	chr2:179602938;179602937;179602936
N2B	4385	13378;13379;13380	chr2:178738211;178738210;178738209	chr2:179602938;179602937;179602936
Novex-1	4510	13753;13754;13755	chr2:178738211;178738210;178738209	chr2:179602938;179602937;179602936
Novex-2	4577	13954;13955;13956	chr2:178738211;178738210;178738209	chr2:179602938;179602937;179602936
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-30
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.226
• 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
I/V	rs753460929	-0.965	0.008	N	0.165	0.08	0.415820034956	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
I/V	rs753460929	-0.965	0.008	N	0.165	0.08	0.415820034956	gnomAD-4.0.0	3.18313E-06	None	None	None	None	N	None	0	0	None	0	2.77932E-05	None	0	0	2.85843E-06	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
I/A	0.7954	likely_pathogenic	0.8817	pathogenic	-1.944	Destabilizing	0.633	D	0.532	neutral	None	None	None	None	N
I/C	0.9104	likely_pathogenic	0.9563	pathogenic	-1.261	Destabilizing	0.996	D	0.663	neutral	None	None	None	None	N
I/D	0.9839	likely_pathogenic	0.9907	pathogenic	-1.23	Destabilizing	0.987	D	0.786	deleterious	None	None	None	None	N
I/E	0.9375	likely_pathogenic	0.9614	pathogenic	-1.173	Destabilizing	0.961	D	0.77	deleterious	None	None	None	None	N
I/F	0.2593	likely_benign	0.3906	ambiguous	-1.341	Destabilizing	0.82	D	0.517	neutral	N	0.481805196	None	None	N
I/G	0.9502	likely_pathogenic	0.9753	pathogenic	-2.333	Highly Destabilizing	0.961	D	0.76	deleterious	None	None	None	None	N
I/H	0.8813	likely_pathogenic	0.9256	pathogenic	-1.571	Destabilizing	0.996	D	0.793	deleterious	None	None	None	None	N
I/K	0.8275	likely_pathogenic	0.8816	pathogenic	-1.234	Destabilizing	0.961	D	0.766	deleterious	None	None	None	None	N
I/L	0.177	likely_benign	0.2262	benign	-0.916	Destabilizing	0.003	N	0.146	neutral	N	0.39908953	None	None	N
I/M	0.1843	likely_benign	0.24	benign	-0.753	Destabilizing	0.901	D	0.524	neutral	N	0.480734311	None	None	N
I/N	0.822	likely_pathogenic	0.8753	pathogenic	-1.113	Destabilizing	0.983	D	0.786	deleterious	N	0.483451722	None	None	N
I/P	0.9761	likely_pathogenic	0.9847	pathogenic	-1.229	Destabilizing	0.987	D	0.789	deleterious	None	None	None	None	N
I/Q	0.8397	likely_pathogenic	0.8902	pathogenic	-1.222	Destabilizing	0.987	D	0.784	deleterious	None	None	None	None	N
I/R	0.7415	likely_pathogenic	0.8281	pathogenic	-0.74	Destabilizing	0.961	D	0.787	deleterious	None	None	None	None	N
I/S	0.782	likely_pathogenic	0.8559	pathogenic	-1.843	Destabilizing	0.901	D	0.678	prob.neutral	N	0.482800732	None	None	N
I/T	0.7101	likely_pathogenic	0.8015	pathogenic	-1.655	Destabilizing	0.722	D	0.597	neutral	N	0.482252887	None	None	N
I/V	0.0991	likely_benign	0.1358	benign	-1.229	Destabilizing	0.008	N	0.165	neutral	N	0.474685462	None	None	N
I/W	0.8908	likely_pathogenic	0.9374	pathogenic	-1.449	Destabilizing	0.996	D	0.797	deleterious	None	None	None	None	N
I/Y	0.7564	likely_pathogenic	0.8254	pathogenic	-1.207	Destabilizing	0.961	D	0.669	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.