TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5385	16378;16379;16380	chr2:178733023;178733022;178733021	chr2:179597750;179597749;179597748
N2AB	5068	15427;15428;15429	chr2:178733023;178733022;178733021	chr2:179597750;179597749;179597748
N2A	4141	12646;12647;12648	chr2:178733023;178733022;178733021	chr2:179597750;179597749;179597748
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-37
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.6707
• Predicted PPI site: I

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
P/A	rs368729048	0.026	0.996	N	0.586	0.421	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
P/A	rs368729048	0.026	0.996	N	0.586	0.421	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/A	rs368729048	0.026	0.996	N	0.586	0.421	None	gnomAD-4.0.0	6.08985E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.22956E-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
P/A	0.7683	likely_pathogenic	0.7814	pathogenic	-0.34	Destabilizing	0.996	D	0.586	neutral	N	0.485679557	None	None	I
P/C	0.9872	likely_pathogenic	0.9881	pathogenic	-0.585	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
P/D	0.9438	likely_pathogenic	0.9511	pathogenic	-0.191	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
P/E	0.9282	likely_pathogenic	0.935	pathogenic	-0.315	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
P/F	0.9861	likely_pathogenic	0.9869	pathogenic	-0.663	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
P/G	0.8904	likely_pathogenic	0.902	pathogenic	-0.442	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/H	0.9186	likely_pathogenic	0.9233	pathogenic	-0.059	Destabilizing	1.0	D	0.671	neutral	N	0.521193731	None	None	I
P/I	0.9747	likely_pathogenic	0.9755	pathogenic	-0.227	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	I
P/K	0.9608	likely_pathogenic	0.9649	pathogenic	-0.297	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/L	0.8442	likely_pathogenic	0.8445	pathogenic	-0.227	Destabilizing	0.998	D	0.665	neutral	N	0.483401832	None	None	I
P/M	0.9706	likely_pathogenic	0.9718	pathogenic	-0.346	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
P/N	0.9317	likely_pathogenic	0.9383	pathogenic	-0.013	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
P/Q	0.8849	likely_pathogenic	0.8935	pathogenic	-0.262	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
P/R	0.8999	likely_pathogenic	0.909	pathogenic	0.186	Stabilizing	1.0	D	0.699	prob.neutral	D	0.526728218	None	None	I
P/S	0.8546	likely_pathogenic	0.862	pathogenic	-0.355	Destabilizing	0.999	D	0.669	neutral	N	0.488237224	None	None	I
P/T	0.8428	likely_pathogenic	0.8453	pathogenic	-0.38	Destabilizing	0.999	D	0.642	neutral	D	0.522282403	None	None	I
P/V	0.9397	likely_pathogenic	0.9418	pathogenic	-0.232	Destabilizing	0.91	D	0.474	neutral	None	None	None	None	I
P/W	0.9919	likely_pathogenic	0.993	pathogenic	-0.731	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
P/Y	0.9797	likely_pathogenic	0.9816	pathogenic	-0.425	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I

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.