TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6840	20743;20744;20745	chr2:178725804;178725803;178725802	chr2:179590531;179590530;179590529
N2AB	6523	19792;19793;19794	chr2:178725804;178725803;178725802	chr2:179590531;179590530;179590529
N2A	5596	17011;17012;17013	chr2:178725804;178725803;178725802	chr2:179590531;179590530;179590529
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-52
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2321
• 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	None	None	1.0	D	0.855	0.684	0.913998194909	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
G/V	rs1413034567	None	1.0	D	0.823	0.668	0.968543987747	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/V	rs1413034567	None	1.0	D	0.823	0.668	0.968543987747	gnomAD-4.0.0	6.57462E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47076E-05	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	0.7302	likely_pathogenic	0.8076	pathogenic	-0.359	Destabilizing	1.0	D	0.74	deleterious	D	0.624058132	None	None	I
G/C	0.9522	likely_pathogenic	0.9621	pathogenic	-0.925	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/D	0.9226	likely_pathogenic	0.9508	pathogenic	-0.86	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
G/E	0.9638	likely_pathogenic	0.9809	pathogenic	-1.036	Destabilizing	1.0	D	0.831	deleterious	D	0.619445199	None	None	I
G/F	0.9873	likely_pathogenic	0.9914	pathogenic	-1.137	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/H	0.9872	likely_pathogenic	0.9919	pathogenic	-0.543	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/I	0.9871	likely_pathogenic	0.9917	pathogenic	-0.561	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
G/K	0.9908	likely_pathogenic	0.9944	pathogenic	-0.905	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/L	0.9835	likely_pathogenic	0.9882	pathogenic	-0.561	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
G/M	0.9909	likely_pathogenic	0.9934	pathogenic	-0.543	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/N	0.9626	likely_pathogenic	0.9743	pathogenic	-0.549	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/P	0.9989	likely_pathogenic	0.9993	pathogenic	-0.463	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/Q	0.9756	likely_pathogenic	0.985	pathogenic	-0.885	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/R	0.9705	likely_pathogenic	0.9817	pathogenic	-0.378	Destabilizing	1.0	D	0.855	deleterious	D	0.629569363	None	None	I
G/S	0.6484	likely_pathogenic	0.7286	pathogenic	-0.642	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/T	0.941	likely_pathogenic	0.9602	pathogenic	-0.761	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/V	0.9716	likely_pathogenic	0.9821	pathogenic	-0.463	Destabilizing	1.0	D	0.823	deleterious	D	0.662647466	None	None	I
G/W	0.9812	likely_pathogenic	0.9875	pathogenic	-1.254	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/Y	0.9805	likely_pathogenic	0.9874	pathogenic	-0.932	Destabilizing	1.0	D	0.826	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.