TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7759	23500;23501;23502	chr2:178720487;178720486;178720485	chr2:179585214;179585213;179585212
N2AB	7442	22549;22550;22551	chr2:178720487;178720486;178720485	chr2:179585214;179585213;179585212
N2A	6515	19768;19769;19770	chr2:178720487;178720486;178720485	chr2:179585214;179585213;179585212
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-62
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0609
• 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
L/I	None	None	0.885	N	0.607	0.443	0.601121310199	gnomAD-4.0.0	2.05283E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79909E-06	1.1595E-05	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
L/A	0.9224	likely_pathogenic	0.9365	pathogenic	-2.615	Highly Destabilizing	0.91	D	0.743	deleterious	None	None	None	None	N
L/C	0.9015	likely_pathogenic	0.9131	pathogenic	-1.625	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.15	Highly Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
L/E	0.9973	likely_pathogenic	0.9981	pathogenic	-2.826	Highly Destabilizing	0.993	D	0.884	deleterious	None	None	None	None	N
L/F	0.5722	likely_pathogenic	0.621	pathogenic	-1.554	Destabilizing	0.1	N	0.453	neutral	D	0.545069474	None	None	N
L/G	0.9915	likely_pathogenic	0.9934	pathogenic	-3.198	Highly Destabilizing	0.993	D	0.88	deleterious	None	None	None	None	N
L/H	0.9909	likely_pathogenic	0.9931	pathogenic	-3.045	Highly Destabilizing	0.999	D	0.872	deleterious	D	0.571785011	None	None	N
L/I	0.1139	likely_benign	0.1263	benign	-0.835	Destabilizing	0.885	D	0.607	neutral	N	0.516569965	None	None	N
L/K	0.9954	likely_pathogenic	0.9968	pathogenic	-1.826	Destabilizing	0.993	D	0.865	deleterious	None	None	None	None	N
L/M	0.27	likely_benign	0.2946	benign	-1.121	Destabilizing	0.993	D	0.637	neutral	None	None	None	None	N
L/N	0.9965	likely_pathogenic	0.9977	pathogenic	-2.601	Highly Destabilizing	0.998	D	0.896	deleterious	None	None	None	None	N
L/P	0.9973	likely_pathogenic	0.9981	pathogenic	-1.424	Destabilizing	0.997	D	0.898	deleterious	D	0.583141316	None	None	N
L/Q	0.9834	likely_pathogenic	0.9882	pathogenic	-2.167	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
L/R	0.9894	likely_pathogenic	0.9922	pathogenic	-2.127	Highly Destabilizing	0.991	D	0.874	deleterious	D	0.583141316	None	None	N
L/S	0.9902	likely_pathogenic	0.9926	pathogenic	-3.018	Highly Destabilizing	0.993	D	0.859	deleterious	None	None	None	None	N
L/T	0.9636	likely_pathogenic	0.9702	pathogenic	-2.527	Highly Destabilizing	0.986	D	0.78	deleterious	None	None	None	None	N
L/V	0.1628	likely_benign	0.1672	benign	-1.424	Destabilizing	0.046	N	0.413	neutral	N	0.520799927	None	None	N
L/W	0.9661	likely_pathogenic	0.9729	pathogenic	-1.828	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
L/Y	0.9685	likely_pathogenic	0.9743	pathogenic	-1.74	Destabilizing	0.973	D	0.77	deleterious	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.