TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26088	78487;78488;78489	chr2:178567870;178567869;178567868	chr2:179432597;179432596;179432595
N2AB	24447	73564;73565;73566	chr2:178567870;178567869;178567868	chr2:179432597;179432596;179432595
N2A	23520	70783;70784;70785	chr2:178567870;178567869;178567868	chr2:179432597;179432596;179432595
N2B	17023	51292;51293;51294	chr2:178567870;178567869;178567868	chr2:179432597;179432596;179432595
Novex-1	17148	51667;51668;51669	chr2:178567870;178567869;178567868	chr2:179432597;179432596;179432595
Novex-2	17215	51868;51869;51870	chr2:178567870;178567869;178567868	chr2:179432597;179432596;179432595
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: Fn3-78
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.8578
• 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/L	None	None	0.999	N	0.734	0.472	0.495238560318	gnomAD-4.0.0	2.05291E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69876E-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	0.1055	likely_benign	0.1377	benign	-0.289	Destabilizing	0.991	D	0.681	prob.neutral	N	0.48778234	None	None	I
P/C	0.6183	likely_pathogenic	0.7052	pathogenic	-0.554	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/D	0.6933	likely_pathogenic	0.7603	pathogenic	-0.153	Destabilizing	0.999	D	0.666	prob.neutral	None	None	None	None	I
P/E	0.4519	ambiguous	0.5541	ambiguous	-0.279	Destabilizing	0.987	D	0.743	deleterious	None	None	None	None	I
P/F	0.6304	likely_pathogenic	0.7425	pathogenic	-0.643	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
P/G	0.5719	likely_pathogenic	0.6751	pathogenic	-0.383	Destabilizing	0.999	D	0.724	deleterious	None	None	None	None	I
P/H	0.3656	ambiguous	0.4543	ambiguous	-0.004	Destabilizing	1.0	D	0.802	deleterious	N	0.517575749	None	None	I
P/I	0.3346	likely_benign	0.4333	ambiguous	-0.198	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/K	0.5165	ambiguous	0.5924	pathogenic	-0.23	Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	I
P/L	0.1614	likely_benign	0.2232	benign	-0.198	Destabilizing	0.999	D	0.734	deleterious	N	0.484566336	None	None	I
P/M	0.395	ambiguous	0.4963	ambiguous	-0.309	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
P/N	0.5366	ambiguous	0.6324	pathogenic	0.057	Stabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
P/Q	0.2582	likely_benign	0.3501	ambiguous	-0.193	Destabilizing	0.969	D	0.516	neutral	None	None	None	None	I
P/R	0.332	likely_benign	0.4044	ambiguous	0.246	Stabilizing	0.997	D	0.797	deleterious	N	0.489556766	None	None	I
P/S	0.2182	likely_benign	0.2894	benign	-0.286	Destabilizing	0.997	D	0.701	prob.delet.	N	0.487190136	None	None	I
P/T	0.1719	likely_benign	0.2307	benign	-0.313	Destabilizing	0.999	D	0.654	prob.neutral	N	0.516308302	None	None	I
P/V	0.2398	likely_benign	0.3091	benign	-0.195	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	I
P/W	0.8604	likely_pathogenic	0.9116	pathogenic	-0.709	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
P/Y	0.663	likely_pathogenic	0.7515	pathogenic	-0.398	Destabilizing	1.0	D	0.807	deleterious	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.