TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2515	7768;7769;7770	chr2:178773513;178773512;178773511	chr2:179638240;179638239;179638238
N2AB	2515	7768;7769;7770	chr2:178773513;178773512;178773511	chr2:179638240;179638239;179638238
N2A	2515	7768;7769;7770	chr2:178773513;178773512;178773511	chr2:179638240;179638239;179638238
N2B	2469	7630;7631;7632	chr2:178773513;178773512;178773511	chr2:179638240;179638239;179638238
Novex-1	2469	7630;7631;7632	chr2:178773513;178773512;178773511	chr2:179638240;179638239;179638238
Novex-2	2469	7630;7631;7632	chr2:178773513;178773512;178773511	chr2:179638240;179638239;179638238
Novex-3	2515	7768;7769;7770	chr2:178773513;178773512;178773511	chr2:179638240;179638239;179638238

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-14
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1155
• 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
Y/H	None	None	0.99	D	0.715	0.823	0.678009228414	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	6.33473E-05	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	0.8297	likely_pathogenic	0.8343	pathogenic	-2.891	Highly Destabilizing	0.754	D	0.783	deleterious	None	None	None	None	N
Y/C	0.162	likely_benign	0.169	benign	-2.139	Highly Destabilizing	0.032	N	0.704	prob.neutral	D	0.783441886	None	None	N
Y/D	0.991	likely_pathogenic	0.9893	pathogenic	-3.524	Highly Destabilizing	0.942	D	0.874	deleterious	D	0.783441886	None	None	N
Y/E	0.9906	likely_pathogenic	0.9895	pathogenic	-3.292	Highly Destabilizing	0.956	D	0.819	deleterious	None	None	None	None	N
Y/F	0.099	likely_benign	0.1109	benign	-1.092	Destabilizing	0.904	D	0.684	prob.neutral	D	0.648698486	None	None	N
Y/G	0.8655	likely_pathogenic	0.8567	pathogenic	-3.344	Highly Destabilizing	0.754	D	0.823	deleterious	None	None	None	None	N
Y/H	0.8353	likely_pathogenic	0.834	pathogenic	-2.246	Highly Destabilizing	0.99	D	0.715	prob.delet.	D	0.784062607	None	None	N
Y/I	0.5113	ambiguous	0.5296	ambiguous	-1.383	Destabilizing	0.956	D	0.759	deleterious	None	None	None	None	N
Y/K	0.9862	likely_pathogenic	0.9848	pathogenic	-2.435	Highly Destabilizing	0.956	D	0.813	deleterious	None	None	None	None	N
Y/L	0.46	ambiguous	0.4606	ambiguous	-1.383	Destabilizing	0.754	D	0.737	prob.delet.	None	None	None	None	N
Y/M	0.7372	likely_pathogenic	0.7526	pathogenic	-1.317	Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
Y/N	0.9126	likely_pathogenic	0.9049	pathogenic	-3.368	Highly Destabilizing	0.942	D	0.849	deleterious	D	0.783441886	None	None	N
Y/P	0.9908	likely_pathogenic	0.9896	pathogenic	-1.902	Destabilizing	0.978	D	0.884	deleterious	None	None	None	None	N
Y/Q	0.9709	likely_pathogenic	0.9695	pathogenic	-3.0	Highly Destabilizing	0.956	D	0.774	deleterious	None	None	None	None	N
Y/R	0.9455	likely_pathogenic	0.9418	pathogenic	-2.405	Highly Destabilizing	0.956	D	0.858	deleterious	None	None	None	None	N
Y/S	0.8246	likely_pathogenic	0.8165	pathogenic	-3.703	Highly Destabilizing	0.125	N	0.681	prob.neutral	D	0.783441886	None	None	N
Y/T	0.8867	likely_pathogenic	0.8876	pathogenic	-3.33	Highly Destabilizing	0.754	D	0.809	deleterious	None	None	None	None	N
Y/V	0.3283	likely_benign	0.3405	ambiguous	-1.902	Destabilizing	0.86	D	0.747	deleterious	None	None	None	None	N
Y/W	0.6231	likely_pathogenic	0.6272	pathogenic	-0.454	Destabilizing	0.998	D	0.718	prob.delet.	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.