TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19265	58018;58019;58020	chr2:178595561;178595560;178595559	chr2:179460288;179460287;179460286
N2AB	17624	53095;53096;53097	chr2:178595561;178595560;178595559	chr2:179460288;179460287;179460286
N2A	16697	50314;50315;50316	chr2:178595561;178595560;178595559	chr2:179460288;179460287;179460286
N2B	10200	30823;30824;30825	chr2:178595561;178595560;178595559	chr2:179460288;179460287;179460286
Novex-1	10325	31198;31199;31200	chr2:178595561;178595560;178595559	chr2:179460288;179460287;179460286
Novex-2	10392	31399;31400;31401	chr2:178595561;178595560;178595559	chr2:179460288;179460287;179460286
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-27
• Domain position: 83
• Structural Position: 115
• Q(SASA): 0.1688
• 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/V	rs1361416773	-0.322	1.0	D	0.887	0.713	0.920238496592	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	2.88018E-04	0	0
G/V	rs1361416773	-0.322	1.0	D	0.887	0.713	0.920238496592	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	9.46E-05	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	0.9327	likely_pathogenic	0.9605	pathogenic	-0.736	Destabilizing	1.0	D	0.757	deleterious	D	0.554808575	None	None	I
G/C	0.9743	likely_pathogenic	0.986	pathogenic	-0.98	Destabilizing	1.0	D	0.869	deleterious	D	0.556076022	None	None	I
G/D	0.9881	likely_pathogenic	0.9941	pathogenic	-1.246	Destabilizing	1.0	D	0.921	deleterious	D	0.536197341	None	None	I
G/E	0.9945	likely_pathogenic	0.9971	pathogenic	-1.389	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	I
G/F	0.9962	likely_pathogenic	0.9978	pathogenic	-1.311	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
G/H	0.9956	likely_pathogenic	0.9976	pathogenic	-1.009	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
G/I	0.9967	likely_pathogenic	0.9978	pathogenic	-0.703	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
G/K	0.9953	likely_pathogenic	0.9974	pathogenic	-1.243	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	I
G/L	0.9949	likely_pathogenic	0.997	pathogenic	-0.703	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
G/M	0.9974	likely_pathogenic	0.9986	pathogenic	-0.51	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	I
G/N	0.9919	likely_pathogenic	0.9953	pathogenic	-0.86	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
G/P	0.9991	likely_pathogenic	0.9993	pathogenic	-0.679	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	I
G/Q	0.9916	likely_pathogenic	0.9956	pathogenic	-1.201	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	I
G/R	0.9837	likely_pathogenic	0.9911	pathogenic	-0.692	Destabilizing	1.0	D	0.919	deleterious	D	0.555062064	None	None	I
G/S	0.8923	likely_pathogenic	0.941	pathogenic	-1.012	Destabilizing	1.0	D	0.861	deleterious	D	0.536197341	None	None	I
G/T	0.9841	likely_pathogenic	0.9898	pathogenic	-1.098	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	I
G/V	0.9935	likely_pathogenic	0.9956	pathogenic	-0.679	Destabilizing	1.0	D	0.887	deleterious	D	0.555315554	None	None	I
G/W	0.9931	likely_pathogenic	0.9963	pathogenic	-1.469	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/Y	0.9955	likely_pathogenic	0.9975	pathogenic	-1.152	Destabilizing	1.0	D	0.887	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.