TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6875	20848;20849;20850	chr2:178725581;178725580;178725579	chr2:179590308;179590307;179590306
N2AB	6558	19897;19898;19899	chr2:178725581;178725580;178725579	chr2:179590308;179590307;179590306
N2A	5631	17116;17117;17118	chr2:178725581;178725580;178725579	chr2:179590308;179590307;179590306
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-53
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1029
• 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
A/T	rs756292622	-1.468	0.576	N	0.449	0.248	0.110078149338	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
A/T	rs756292622	-1.468	0.576	N	0.449	0.248	0.110078149338	gnomAD-4.0.0	2.05493E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80018E-06	1.16452E-05	0
A/V	rs199875225	None	0.978	N	0.696	0.277	0.227934060464	gnomAD-4.0.0	1.59542E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86438E-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
A/C	0.5825	likely_pathogenic	0.5431	ambiguous	-1.309	Destabilizing	0.491	N	0.543	neutral	None	None	None	None	N
A/D	0.917	likely_pathogenic	0.9281	pathogenic	-2.233	Highly Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	N
A/E	0.8901	likely_pathogenic	0.9129	pathogenic	-2.069	Highly Destabilizing	0.997	D	0.798	deleterious	N	0.484129171	None	None	N
A/F	0.6738	likely_pathogenic	0.6996	pathogenic	-0.743	Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
A/G	0.2429	likely_benign	0.2501	benign	-1.501	Destabilizing	0.989	D	0.694	prob.neutral	N	0.491977273	None	None	N
A/H	0.9491	likely_pathogenic	0.9507	pathogenic	-1.868	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
A/I	0.4152	ambiguous	0.4065	ambiguous	0.15	Stabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
A/K	0.9652	likely_pathogenic	0.975	pathogenic	-1.148	Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
A/L	0.3834	ambiguous	0.3989	ambiguous	0.15	Stabilizing	0.983	D	0.765	deleterious	None	None	None	None	N
A/M	0.4455	ambiguous	0.4427	ambiguous	-0.167	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
A/N	0.8431	likely_pathogenic	0.8335	pathogenic	-1.391	Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
A/P	0.9608	likely_pathogenic	0.9752	pathogenic	-0.205	Destabilizing	0.999	D	0.803	deleterious	N	0.484129171	None	None	N
A/Q	0.895	likely_pathogenic	0.9077	pathogenic	-1.262	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
A/R	0.9413	likely_pathogenic	0.956	pathogenic	-1.183	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
A/S	0.2282	likely_benign	0.2004	benign	-1.821	Destabilizing	0.956	D	0.686	prob.neutral	N	0.483622192	None	None	N
A/T	0.1416	likely_benign	0.1318	benign	-1.531	Destabilizing	0.576	D	0.449	neutral	N	0.467118901	None	None	N
A/V	0.1635	likely_benign	0.1666	benign	-0.205	Destabilizing	0.978	D	0.696	prob.neutral	N	0.498476384	None	None	N
A/W	0.9683	likely_pathogenic	0.9735	pathogenic	-1.449	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
A/Y	0.8673	likely_pathogenic	0.8792	pathogenic	-0.898	Destabilizing	0.999	D	0.884	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.