TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26242	78949;78950;78951	chr2:178567408;178567407;178567406	chr2:179432135;179432134;179432133
N2AB	24601	74026;74027;74028	chr2:178567408;178567407;178567406	chr2:179432135;179432134;179432133
N2A	23674	71245;71246;71247	chr2:178567408;178567407;178567406	chr2:179432135;179432134;179432133
N2B	17177	51754;51755;51756	chr2:178567408;178567407;178567406	chr2:179432135;179432134;179432133
Novex-1	17302	52129;52130;52131	chr2:178567408;178567407;178567406	chr2:179432135;179432134;179432133
Novex-2	17369	52330;52331;52332	chr2:178567408;178567407;178567406	chr2:179432135;179432134;179432133
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-137
• Domain position: 50
• Structural Position: 123
• Q(SASA): 0.2086
• 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	0.684	N	0.495	0.559	0.682517699708	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	rs750748102	None	0.645	D	0.405	0.274	0.532503582573	gnomAD-4.0.0	1.61667E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89088E-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	0.8403	likely_pathogenic	0.7689	pathogenic	-2.304	Highly Destabilizing	0.742	D	0.435	neutral	None	None	None	None	N
I/C	0.8772	likely_pathogenic	0.8266	pathogenic	-1.355	Destabilizing	0.996	D	0.561	neutral	None	None	None	None	N
I/D	0.9753	likely_pathogenic	0.9631	pathogenic	-2.166	Highly Destabilizing	0.835	D	0.587	neutral	None	None	None	None	N
I/E	0.8839	likely_pathogenic	0.8496	pathogenic	-2.076	Highly Destabilizing	0.742	D	0.58	neutral	None	None	None	None	N
I/F	0.3405	ambiguous	0.2714	benign	-1.484	Destabilizing	0.984	D	0.52	neutral	None	None	None	None	N
I/G	0.9418	likely_pathogenic	0.9126	pathogenic	-2.733	Highly Destabilizing	0.742	D	0.576	neutral	None	None	None	None	N
I/H	0.8656	likely_pathogenic	0.8045	pathogenic	-2.018	Highly Destabilizing	0.987	D	0.675	prob.neutral	None	None	None	None	N
I/K	0.6345	likely_pathogenic	0.5614	ambiguous	-1.783	Destabilizing	0.521	D	0.572	neutral	D	0.522616217	None	None	N
I/L	0.2421	likely_benign	0.1977	benign	-1.129	Destabilizing	0.472	N	0.375	neutral	N	0.488365809	None	None	N
I/M	0.1492	likely_benign	0.1274	benign	-0.816	Destabilizing	0.979	D	0.515	neutral	D	0.53125139	None	None	N
I/N	0.7435	likely_pathogenic	0.6675	pathogenic	-1.701	Destabilizing	0.037	N	0.439	neutral	None	None	None	None	N
I/P	0.9761	likely_pathogenic	0.9661	pathogenic	-1.495	Destabilizing	0.984	D	0.667	neutral	None	None	None	None	N
I/Q	0.7557	likely_pathogenic	0.6856	pathogenic	-1.786	Destabilizing	0.91	D	0.651	neutral	None	None	None	None	N
I/R	0.5894	likely_pathogenic	0.5033	ambiguous	-1.211	Destabilizing	0.015	N	0.445	neutral	D	0.52698431	None	None	N
I/S	0.8187	likely_pathogenic	0.7416	pathogenic	-2.343	Highly Destabilizing	0.742	D	0.531	neutral	None	None	None	None	N
I/T	0.7355	likely_pathogenic	0.6116	pathogenic	-2.133	Highly Destabilizing	0.684	D	0.495	neutral	N	0.50613135	None	None	N
I/V	0.1386	likely_benign	0.1194	benign	-1.495	Destabilizing	0.645	D	0.405	neutral	D	0.527264148	None	None	N
I/W	0.863	likely_pathogenic	0.8004	pathogenic	-1.712	Destabilizing	0.996	D	0.688	prob.neutral	None	None	None	None	N
I/Y	0.7227	likely_pathogenic	0.6608	pathogenic	-1.499	Destabilizing	0.984	D	0.593	neutral	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.