TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9186	27781;27782;27783	chr2:178712366;178712365;178712364	chr2:179577093;179577092;179577091
N2AB	8869	26830;26831;26832	chr2:178712366;178712365;178712364	chr2:179577093;179577092;179577091
N2A	7942	24049;24050;24051	chr2:178712366;178712365;178712364	chr2:179577093;179577092;179577091
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-77
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0797
• 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/T	None	None	0.801	N	0.727	0.386	0.720015287893	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/V	rs781132732	-1.446	0.005	N	0.256	0.087	0.478527412683	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs781132732	-1.446	0.005	N	0.256	0.087	0.478527412683	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06697E-04	0
I/V	rs781132732	-1.446	0.005	N	0.256	0.087	0.478527412683	gnomAD-4.0.0	7.68624E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.04096E-05	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	0.4931	ambiguous	0.4075	ambiguous	-2.926	Highly Destabilizing	0.525	D	0.684	prob.neutral	None	None	None	None	N
I/C	0.9373	likely_pathogenic	0.9161	pathogenic	-2.267	Highly Destabilizing	0.998	D	0.782	deleterious	None	None	None	None	N
I/D	0.9972	likely_pathogenic	0.9963	pathogenic	-3.475	Highly Destabilizing	0.991	D	0.858	deleterious	None	None	None	None	N
I/E	0.99	likely_pathogenic	0.9887	pathogenic	-3.193	Highly Destabilizing	0.974	D	0.85	deleterious	None	None	None	None	N
I/F	0.78	likely_pathogenic	0.695	pathogenic	-1.67	Destabilizing	0.934	D	0.775	deleterious	N	0.493658955	None	None	N
I/G	0.961	likely_pathogenic	0.9471	pathogenic	-3.491	Highly Destabilizing	0.974	D	0.832	deleterious	None	None	None	None	N
I/H	0.9936	likely_pathogenic	0.9915	pathogenic	-2.995	Highly Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
I/K	0.9851	likely_pathogenic	0.9827	pathogenic	-2.149	Highly Destabilizing	0.974	D	0.832	deleterious	None	None	None	None	N
I/L	0.261	likely_benign	0.2263	benign	-1.243	Destabilizing	0.005	N	0.291	neutral	N	0.495733307	None	None	N
I/M	0.28	likely_benign	0.2259	benign	-1.492	Destabilizing	0.934	D	0.733	prob.delet.	N	0.484442243	None	None	N
I/N	0.9694	likely_pathogenic	0.9642	pathogenic	-2.7	Highly Destabilizing	0.989	D	0.854	deleterious	N	0.516625055	None	None	N
I/P	0.991	likely_pathogenic	0.988	pathogenic	-1.793	Destabilizing	0.991	D	0.855	deleterious	None	None	None	None	N
I/Q	0.9842	likely_pathogenic	0.9805	pathogenic	-2.448	Highly Destabilizing	0.991	D	0.851	deleterious	None	None	None	None	N
I/R	0.9692	likely_pathogenic	0.9661	pathogenic	-2.013	Highly Destabilizing	0.991	D	0.857	deleterious	None	None	None	None	N
I/S	0.8312	likely_pathogenic	0.7881	pathogenic	-3.31	Highly Destabilizing	0.966	D	0.811	deleterious	N	0.483935264	None	None	N
I/T	0.4596	ambiguous	0.3565	ambiguous	-2.881	Highly Destabilizing	0.801	D	0.727	prob.delet.	N	0.489366541	None	None	N
I/V	0.0894	likely_benign	0.0774	benign	-1.793	Destabilizing	0.005	N	0.256	neutral	N	0.409570186	None	None	N
I/W	0.9957	likely_pathogenic	0.9932	pathogenic	-2.062	Highly Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
I/Y	0.9837	likely_pathogenic	0.9785	pathogenic	-1.875	Destabilizing	0.991	D	0.819	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.