TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6551	19876;19877;19878	chr2:178728173;178728172;178728171	chr2:179592900;179592899;179592898
N2AB	6234	18925;18926;18927	chr2:178728173;178728172;178728171	chr2:179592900;179592899;179592898
N2A	5307	16144;16145;16146	chr2:178728173;178728172;178728171	chr2:179592900;179592899;179592898
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-49
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.0964
• 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
Y/C	None	None	1.0	D	0.873	0.902	0.815021892448	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Y/H	None	None	1.0	D	0.775	0.884	0.681102614202	gnomAD-4.0.0	1.59671E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03361E-05

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
Y/A	0.9943	likely_pathogenic	0.9963	pathogenic	-2.828	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/C	0.8977	likely_pathogenic	0.943	pathogenic	-2.34	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.660388335	None	None	N
Y/D	0.9961	likely_pathogenic	0.9971	pathogenic	-3.45	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.660388335	None	None	N
Y/E	0.9986	likely_pathogenic	0.9991	pathogenic	-3.215	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/F	0.1516	likely_benign	0.1629	benign	-1.101	Destabilizing	0.999	D	0.663	neutral	D	0.567392109	None	None	N
Y/G	0.9908	likely_pathogenic	0.9929	pathogenic	-3.288	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/H	0.9598	likely_pathogenic	0.9778	pathogenic	-2.357	Highly Destabilizing	1.0	D	0.775	deleterious	D	0.660186531	None	None	N
Y/I	0.8325	likely_pathogenic	0.8912	pathogenic	-1.299	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Y/K	0.9981	likely_pathogenic	0.9988	pathogenic	-2.326	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/L	0.843	likely_pathogenic	0.8725	pathogenic	-1.299	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
Y/M	0.9643	likely_pathogenic	0.9759	pathogenic	-1.415	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
Y/N	0.9822	likely_pathogenic	0.987	pathogenic	-3.243	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.660388335	None	None	N
Y/P	0.9989	likely_pathogenic	0.9991	pathogenic	-1.826	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.9987	pathogenic	-2.865	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
Y/R	0.9932	likely_pathogenic	0.9954	pathogenic	-2.332	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
Y/S	0.9857	likely_pathogenic	0.99	pathogenic	-3.605	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.660388335	None	None	N
Y/T	0.9922	likely_pathogenic	0.995	pathogenic	-3.224	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/V	0.7985	likely_pathogenic	0.8571	pathogenic	-1.826	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
Y/W	0.782	likely_pathogenic	0.852	pathogenic	-0.468	Destabilizing	1.0	D	0.77	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.