TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34171	102736;102737;102738	chr2:178534104;178534103;178534102	chr2:179398831;179398830;179398829
N2AB	32530	97813;97814;97815	chr2:178534104;178534103;178534102	chr2:179398831;179398830;179398829
N2A	31603	95032;95033;95034	chr2:178534104;178534103;178534102	chr2:179398831;179398830;179398829
N2B	25106	75541;75542;75543	chr2:178534104;178534103;178534102	chr2:179398831;179398830;179398829
Novex-1	25231	75916;75917;75918	chr2:178534104;178534103;178534102	chr2:179398831;179398830;179398829
Novex-2	25298	76117;76118;76119	chr2:178534104;178534103;178534102	chr2:179398831;179398830;179398829
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-160
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.187
• 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
Y/C	None	None	1.0	N	0.783	0.529	0.61879682266	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9695	likely_pathogenic	0.9598	pathogenic	-2.874	Highly Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
Y/C	0.7974	likely_pathogenic	0.7851	pathogenic	-1.26	Destabilizing	1.0	D	0.783	deleterious	N	0.4796494	None	None	I
Y/D	0.9466	likely_pathogenic	0.9244	pathogenic	-1.761	Destabilizing	1.0	D	0.785	deleterious	N	0.479395911	None	None	I
Y/E	0.9821	likely_pathogenic	0.9732	pathogenic	-1.651	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
Y/F	0.1871	likely_benign	0.1893	benign	-1.22	Destabilizing	0.999	D	0.532	neutral	N	0.442143098	None	None	I
Y/G	0.9491	likely_pathogenic	0.9365	pathogenic	-3.206	Highly Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
Y/H	0.6649	likely_pathogenic	0.623	pathogenic	-1.433	Destabilizing	1.0	D	0.755	deleterious	N	0.46120275	None	None	I
Y/I	0.9274	likely_pathogenic	0.9048	pathogenic	-1.827	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
Y/K	0.9782	likely_pathogenic	0.9693	pathogenic	-1.459	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
Y/L	0.87	likely_pathogenic	0.8484	pathogenic	-1.827	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	I
Y/M	0.9317	likely_pathogenic	0.9119	pathogenic	-1.416	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
Y/N	0.7364	likely_pathogenic	0.6806	pathogenic	-1.759	Destabilizing	1.0	D	0.775	deleterious	N	0.46145624	None	None	I
Y/P	0.999	likely_pathogenic	0.9986	pathogenic	-2.178	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
Y/Q	0.9643	likely_pathogenic	0.9509	pathogenic	-1.746	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
Y/R	0.9488	likely_pathogenic	0.932	pathogenic	-0.901	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
Y/S	0.8328	likely_pathogenic	0.7907	pathogenic	-2.326	Highly Destabilizing	1.0	D	0.749	deleterious	N	0.47346887	None	None	I
Y/T	0.9475	likely_pathogenic	0.927	pathogenic	-2.125	Highly Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
Y/V	0.8998	likely_pathogenic	0.8724	pathogenic	-2.178	Highly Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
Y/W	0.7449	likely_pathogenic	0.7304	pathogenic	-0.604	Destabilizing	1.0	D	0.741	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.