TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32803	98632;98633;98634	chr2:178539658;178539657;178539656	chr2:179404385;179404384;179404383
N2AB	31162	93709;93710;93711	chr2:178539658;178539657;178539656	chr2:179404385;179404384;179404383
N2A	30235	90928;90929;90930	chr2:178539658;178539657;178539656	chr2:179404385;179404384;179404383
N2B	23738	71437;71438;71439	chr2:178539658;178539657;178539656	chr2:179404385;179404384;179404383
Novex-1	23863	71812;71813;71814	chr2:178539658;178539657;178539656	chr2:179404385;179404384;179404383
Novex-2	23930	72013;72014;72015	chr2:178539658;178539657;178539656	chr2:179404385;179404384;179404383
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-127
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.1742
• 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/P	None	None	1.0	N	0.885	0.571	0.722748815689	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85799E-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
L/A	0.9163	likely_pathogenic	0.918	pathogenic	-2.356	Highly Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
L/C	0.9481	likely_pathogenic	0.9391	pathogenic	-1.631	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.9987	pathogenic	-2.348	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/E	0.9905	likely_pathogenic	0.9908	pathogenic	-2.117	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/F	0.6286	likely_pathogenic	0.5922	pathogenic	-1.278	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/G	0.9895	likely_pathogenic	0.9899	pathogenic	-2.91	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/H	0.9869	likely_pathogenic	0.9851	pathogenic	-2.361	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/I	0.1801	likely_benign	0.1667	benign	-0.76	Destabilizing	0.999	D	0.66	neutral	None	None	None	None	N
L/K	0.9838	likely_pathogenic	0.9838	pathogenic	-1.717	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/M	0.3233	likely_benign	0.3065	benign	-0.795	Destabilizing	1.0	D	0.793	deleterious	N	0.486867644	None	None	N
L/N	0.9938	likely_pathogenic	0.9931	pathogenic	-2.004	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/P	0.9407	likely_pathogenic	0.9322	pathogenic	-1.271	Destabilizing	1.0	D	0.885	deleterious	N	0.490823346	None	None	N
L/Q	0.9697	likely_pathogenic	0.9694	pathogenic	-1.841	Destabilizing	1.0	D	0.877	deleterious	N	0.515860906	None	None	N
L/R	0.9716	likely_pathogenic	0.9727	pathogenic	-1.529	Destabilizing	1.0	D	0.877	deleterious	N	0.500883749	None	None	N
L/S	0.9867	likely_pathogenic	0.9858	pathogenic	-2.748	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/T	0.9245	likely_pathogenic	0.9171	pathogenic	-2.367	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/V	0.2381	likely_benign	0.2187	benign	-1.271	Destabilizing	0.999	D	0.66	neutral	N	0.441314458	None	None	N
L/W	0.9217	likely_pathogenic	0.9209	pathogenic	-1.635	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
L/Y	0.9686	likely_pathogenic	0.9653	pathogenic	-1.339	Destabilizing	1.0	D	0.841	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.