TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	991	3196;3197;3198	chr2:178782935;178782934;178782933	chr2:179647662;179647661;179647660
N2AB	991	3196;3197;3198	chr2:178782935;178782934;178782933	chr2:179647662;179647661;179647660
N2A	991	3196;3197;3198	chr2:178782935;178782934;178782933	chr2:179647662;179647661;179647660
N2B	945	3058;3059;3060	chr2:178782935;178782934;178782933	chr2:179647662;179647661;179647660
Novex-1	945	3058;3059;3060	chr2:178782935;178782934;178782933	chr2:179647662;179647661;179647660
Novex-2	945	3058;3059;3060	chr2:178782935;178782934;178782933	chr2:179647662;179647661;179647660
Novex-3	991	3196;3197;3198	chr2:178782935;178782934;178782933	chr2:179647662;179647661;179647660

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-3
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.1961
• 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
I/M	None	None	0.075	D	0.4	0.358	0.394230963961	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.952	likely_pathogenic	0.9593	pathogenic	-1.948	Destabilizing	0.415	N	0.538	neutral	None	None	None	None	I
I/C	0.9699	likely_pathogenic	0.9739	pathogenic	-1.254	Destabilizing	0.996	D	0.609	neutral	None	None	None	None	I
I/D	0.9923	likely_pathogenic	0.9938	pathogenic	-1.261	Destabilizing	0.961	D	0.705	prob.neutral	None	None	None	None	I
I/E	0.972	likely_pathogenic	0.9761	pathogenic	-1.182	Destabilizing	0.961	D	0.705	prob.neutral	None	None	None	None	I
I/F	0.6148	likely_pathogenic	0.6334	pathogenic	-1.275	Destabilizing	0.923	D	0.503	neutral	None	None	None	None	I
I/G	0.9893	likely_pathogenic	0.9914	pathogenic	-2.363	Highly Destabilizing	0.961	D	0.682	prob.neutral	None	None	None	None	I
I/H	0.966	likely_pathogenic	0.9735	pathogenic	-1.615	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	I
I/K	0.895	likely_pathogenic	0.9137	pathogenic	-1.304	Destabilizing	0.901	D	0.687	prob.neutral	D	0.606420224	None	None	I
I/L	0.3877	ambiguous	0.4057	ambiguous	-0.839	Destabilizing	0.075	N	0.361	neutral	N	0.49834967	None	None	I
I/M	0.218	likely_benign	0.2348	benign	-0.693	Destabilizing	0.075	N	0.4	neutral	D	0.548498496	None	None	I
I/N	0.9067	likely_pathogenic	0.9199	pathogenic	-1.225	Destabilizing	0.961	D	0.717	prob.delet.	None	None	None	None	I
I/P	0.9906	likely_pathogenic	0.9926	pathogenic	-1.179	Destabilizing	0.987	D	0.723	prob.delet.	None	None	None	None	I
I/Q	0.9319	likely_pathogenic	0.9455	pathogenic	-1.284	Destabilizing	0.961	D	0.733	prob.delet.	None	None	None	None	I
I/R	0.8918	likely_pathogenic	0.9135	pathogenic	-0.851	Destabilizing	0.901	D	0.724	prob.delet.	D	0.565203256	None	None	I
I/S	0.9477	likely_pathogenic	0.9568	pathogenic	-1.951	Destabilizing	0.633	D	0.625	neutral	None	None	None	None	I
I/T	0.9131	likely_pathogenic	0.919	pathogenic	-1.734	Destabilizing	0.034	N	0.367	neutral	D	0.546292518	None	None	I
I/V	0.247	likely_benign	0.2488	benign	-1.179	Destabilizing	0.19	N	0.389	neutral	N	0.50421009	None	None	I
I/W	0.9779	likely_pathogenic	0.9827	pathogenic	-1.413	Destabilizing	0.996	D	0.75	deleterious	None	None	None	None	I
I/Y	0.9114	likely_pathogenic	0.9211	pathogenic	-1.165	Destabilizing	0.961	D	0.617	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.