TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6537	19834;19835;19836	chr2:178728215;178728214;178728213	chr2:179592942;179592941;179592940
N2AB	6220	18883;18884;18885	chr2:178728215;178728214;178728213	chr2:179592942;179592941;179592940
N2A	5293	16102;16103;16104	chr2:178728215;178728214;178728213	chr2:179592942;179592941;179592940
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-49
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1591
• 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
S/P	None	None	0.782	N	0.709	0.507	0.367229591828	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

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
S/A	0.0832	likely_benign	0.0771	benign	-0.492	Destabilizing	0.003	N	0.323	neutral	N	0.494887945	None	None	N
S/C	0.1339	likely_benign	0.1488	benign	-0.386	Destabilizing	0.965	D	0.723	prob.delet.	D	0.532195539	None	None	N
S/D	0.4842	ambiguous	0.5327	ambiguous	-1.717	Destabilizing	0.575	D	0.607	neutral	None	None	None	None	N
S/E	0.537	ambiguous	0.5422	ambiguous	-1.478	Destabilizing	0.575	D	0.625	neutral	None	None	None	None	N
S/F	0.1186	likely_benign	0.1249	benign	-0.249	Destabilizing	0.879	D	0.773	deleterious	N	0.512820345	None	None	N
S/G	0.1535	likely_benign	0.1671	benign	-0.916	Destabilizing	0.404	N	0.601	neutral	None	None	None	None	N
S/H	0.3241	likely_benign	0.35	ambiguous	-1.442	Destabilizing	0.991	D	0.726	prob.delet.	None	None	None	None	N
S/I	0.1505	likely_benign	0.1445	benign	0.6	Stabilizing	0.826	D	0.737	prob.delet.	None	None	None	None	N
S/K	0.686	likely_pathogenic	0.7089	pathogenic	-0.135	Destabilizing	0.575	D	0.623	neutral	None	None	None	None	N
S/L	0.0926	likely_benign	0.088	benign	0.6	Stabilizing	0.404	N	0.701	prob.neutral	None	None	None	None	N
S/M	0.1906	likely_benign	0.1818	benign	0.376	Stabilizing	0.973	D	0.729	prob.delet.	None	None	None	None	N
S/N	0.2232	likely_benign	0.2412	benign	-1.048	Destabilizing	0.733	D	0.588	neutral	None	None	None	None	N
S/P	0.8613	likely_pathogenic	0.8893	pathogenic	0.271	Stabilizing	0.782	D	0.709	prob.delet.	N	0.519791834	None	None	N
S/Q	0.5048	ambiguous	0.511	ambiguous	-0.597	Destabilizing	0.906	D	0.671	neutral	None	None	None	None	N
S/R	0.567	likely_pathogenic	0.6002	pathogenic	-0.785	Destabilizing	0.826	D	0.725	prob.delet.	None	None	None	None	N
S/T	0.0874	likely_benign	0.0866	benign	-0.55	Destabilizing	0.013	N	0.446	neutral	N	0.444666981	None	None	N
S/V	0.1606	likely_benign	0.1509	benign	0.271	Stabilizing	0.404	N	0.709	prob.delet.	None	None	None	None	N
S/W	0.2459	likely_benign	0.2703	benign	-0.778	Destabilizing	0.991	D	0.782	deleterious	None	None	None	None	N
S/Y	0.1272	likely_benign	0.1416	benign	-0.229	Destabilizing	0.957	D	0.777	deleterious	N	0.491812531	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.