TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8805	26638;26639;26640	chr2:178714361;178714360;178714359	chr2:179579088;179579087;179579086
N2AB	8488	25687;25688;25689	chr2:178714361;178714360;178714359	chr2:179579088;179579087;179579086
N2A	7561	22906;22907;22908	chr2:178714361;178714360;178714359	chr2:179579088;179579087;179579086
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-73
• Domain position: 70
• Structural Position: 152
• Q(SASA): 0.1962
• 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
G/R	rs756620595	-0.443	1.0	D	0.823	0.705	0.890888985325	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
G/R	rs756620595	-0.443	1.0	D	0.823	0.705	0.890888985325	gnomAD-4.0.0	1.59136E-06	None	None	None	None	I	None	5.65867E-05	0	None	0	0	None	0	0	0	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
G/A	0.3055	likely_benign	0.4165	ambiguous	-0.573	Destabilizing	1.0	D	0.737	prob.delet.	D	0.582131	None	None	I
G/C	0.7038	likely_pathogenic	0.8491	pathogenic	-0.836	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
G/D	0.772	likely_pathogenic	0.8672	pathogenic	-0.608	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/E	0.8006	likely_pathogenic	0.8947	pathogenic	-0.677	Destabilizing	1.0	D	0.83	deleterious	D	0.647872881	None	None	I
G/F	0.9492	likely_pathogenic	0.9744	pathogenic	-0.964	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
G/H	0.9243	likely_pathogenic	0.9657	pathogenic	-1.13	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
G/I	0.9266	likely_pathogenic	0.9725	pathogenic	-0.238	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/K	0.9091	likely_pathogenic	0.9605	pathogenic	-0.995	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/L	0.8916	likely_pathogenic	0.9522	pathogenic	-0.238	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
G/M	0.9171	likely_pathogenic	0.965	pathogenic	-0.228	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
G/N	0.8298	likely_pathogenic	0.9175	pathogenic	-0.666	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/P	0.992	likely_pathogenic	0.9957	pathogenic	-0.308	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/Q	0.8152	likely_pathogenic	0.9072	pathogenic	-0.825	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/R	0.7889	likely_pathogenic	0.8925	pathogenic	-0.732	Destabilizing	1.0	D	0.823	deleterious	D	0.647671077	None	None	I
G/S	0.2623	likely_benign	0.4079	ambiguous	-0.984	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/T	0.7404	likely_pathogenic	0.8703	pathogenic	-0.958	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
G/V	0.8357	likely_pathogenic	0.9277	pathogenic	-0.308	Destabilizing	1.0	D	0.8	deleterious	D	0.647872881	None	None	I
G/W	0.9089	likely_pathogenic	0.9565	pathogenic	-1.295	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
G/Y	0.9355	likely_pathogenic	0.9716	pathogenic	-0.862	Destabilizing	1.0	D	0.773	deleterious	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.