TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32660	98203;98204;98205	chr2:178540188;178540187;178540186	chr2:179404915;179404914;179404913
N2AB	31019	93280;93281;93282	chr2:178540188;178540187;178540186	chr2:179404915;179404914;179404913
N2A	30092	90499;90500;90501	chr2:178540188;178540187;178540186	chr2:179404915;179404914;179404913
N2B	23595	71008;71009;71010	chr2:178540188;178540187;178540186	chr2:179404915;179404914;179404913
Novex-1	23720	71383;71384;71385	chr2:178540188;178540187;178540186	chr2:179404915;179404914;179404913
Novex-2	23787	71584;71585;71586	chr2:178540188;178540187;178540186	chr2:179404915;179404914;179404913
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-126
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.2107
• 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/H	rs781416687	-1.105	1.0	N	0.749	0.504	0.512766428439	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/H	rs781416687	-1.105	1.0	N	0.749	0.504	0.512766428439	gnomAD-4.0.0	6.58137E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47115E-05	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	0.9829	likely_pathogenic	0.9719	pathogenic	-2.253	Highly Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
Y/C	0.8268	likely_pathogenic	0.7353	pathogenic	-1.301	Destabilizing	1.0	D	0.831	deleterious	N	0.520100529	None	None	I
Y/D	0.9842	likely_pathogenic	0.975	pathogenic	-1.24	Destabilizing	1.0	D	0.851	deleterious	D	0.530284041	None	None	I
Y/E	0.995	likely_pathogenic	0.9908	pathogenic	-1.094	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
Y/F	0.2215	likely_benign	0.195	benign	-0.753	Destabilizing	0.999	D	0.541	neutral	N	0.438271366	None	None	I
Y/G	0.9606	likely_pathogenic	0.9525	pathogenic	-2.623	Highly Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
Y/H	0.9319	likely_pathogenic	0.8807	pathogenic	-1.074	Destabilizing	1.0	D	0.749	deleterious	N	0.476020501	None	None	I
Y/I	0.9647	likely_pathogenic	0.9328	pathogenic	-1.101	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
Y/K	0.9915	likely_pathogenic	0.9847	pathogenic	-1.513	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
Y/L	0.9356	likely_pathogenic	0.9024	pathogenic	-1.101	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	I
Y/M	0.9526	likely_pathogenic	0.9212	pathogenic	-0.93	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
Y/N	0.9413	likely_pathogenic	0.9036	pathogenic	-2.06	Highly Destabilizing	1.0	D	0.824	deleterious	D	0.530030551	None	None	I
Y/P	0.9996	likely_pathogenic	0.9993	pathogenic	-1.485	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
Y/Q	0.9919	likely_pathogenic	0.983	pathogenic	-1.831	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
Y/R	0.9858	likely_pathogenic	0.9753	pathogenic	-1.277	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
Y/S	0.9721	likely_pathogenic	0.9531	pathogenic	-2.581	Highly Destabilizing	1.0	D	0.78	deleterious	N	0.500316501	None	None	I
Y/T	0.9851	likely_pathogenic	0.9733	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
Y/V	0.9371	likely_pathogenic	0.8941	pathogenic	-1.485	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
Y/W	0.8728	likely_pathogenic	0.8391	pathogenic	-0.267	Destabilizing	1.0	D	0.734	prob.delet.	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.