TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7999	24220;24221;24222	chr2:178719395;178719394;178719393	chr2:179584122;179584121;179584120
N2AB	7682	23269;23270;23271	chr2:178719395;178719394;178719393	chr2:179584122;179584121;179584120
N2A	6755	20488;20489;20490	chr2:178719395;178719394;178719393	chr2:179584122;179584121;179584120
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: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-65
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3103
• 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/A	rs750389762	-0.27	1.0	D	0.791	0.571	0.661045744637	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
G/A	rs750389762	-0.27	1.0	D	0.791	0.571	0.661045744637	gnomAD-4.0.0	1.59148E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41546E-04	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	0.1913	likely_benign	0.2219	benign	-0.24	Destabilizing	1.0	D	0.791	deleterious	D	0.604556301	None	None	I
G/C	0.3764	ambiguous	0.4133	ambiguous	-0.883	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
G/D	0.1469	likely_benign	0.1629	benign	-0.138	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
G/E	0.1945	likely_benign	0.2309	benign	-0.266	Destabilizing	1.0	D	0.86	deleterious	D	0.596410896	None	None	I
G/F	0.6237	likely_pathogenic	0.6687	pathogenic	-0.752	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/H	0.2957	likely_benign	0.3443	ambiguous	-0.47	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
G/I	0.5804	likely_pathogenic	0.6591	pathogenic	-0.243	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
G/K	0.3444	ambiguous	0.3913	ambiguous	-0.766	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
G/L	0.5005	ambiguous	0.5698	pathogenic	-0.243	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
G/M	0.6008	likely_pathogenic	0.655	pathogenic	-0.435	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/N	0.2134	likely_benign	0.2268	benign	-0.5	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/P	0.8216	likely_pathogenic	0.8796	pathogenic	-0.206	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
G/Q	0.2874	likely_benign	0.3364	benign	-0.688	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	I
G/R	0.2535	likely_benign	0.2909	benign	-0.423	Destabilizing	1.0	D	0.883	deleterious	D	0.625188595	None	None	I
G/S	0.127	likely_benign	0.1434	benign	-0.735	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/T	0.2648	likely_benign	0.3083	benign	-0.773	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/V	0.4212	ambiguous	0.4931	ambiguous	-0.206	Destabilizing	1.0	D	0.845	deleterious	D	0.646517382	None	None	I
G/W	0.4824	ambiguous	0.5326	ambiguous	-0.962	Destabilizing	1.0	D	0.863	deleterious	D	0.646719186	None	None	I
G/Y	0.4321	ambiguous	0.4695	ambiguous	-0.587	Destabilizing	1.0	D	0.862	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.