TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5483	16672;16673;16674	chr2:178732614;178732613;178732612	chr2:179597341;179597340;179597339
N2AB	5166	15721;15722;15723	chr2:178732614;178732613;178732612	chr2:179597341;179597340;179597339
N2A	4239	12940;12941;12942	chr2:178732614;178732613;178732612	chr2:179597341;179597340;179597339
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-38
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1302
• 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
W/R	rs72648938	None	0.999	D	0.865	0.963	0.968585133873	gnomAD-4.0.0	1.36861E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79904E-06	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
W/A	0.9923	likely_pathogenic	0.9942	pathogenic	-3.241	Highly Destabilizing	0.996	D	0.841	deleterious	None	None	None	None	N
W/C	0.9936	likely_pathogenic	0.995	pathogenic	-1.658	Destabilizing	1.0	D	0.826	deleterious	D	0.710494721	None	None	N
W/D	0.999	likely_pathogenic	0.9991	pathogenic	-3.477	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
W/E	0.9987	likely_pathogenic	0.9989	pathogenic	-3.361	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
W/F	0.654	likely_pathogenic	0.736	pathogenic	-2.053	Highly Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
W/G	0.9659	likely_pathogenic	0.9712	pathogenic	-3.475	Highly Destabilizing	0.999	D	0.826	deleterious	D	0.710292917	None	None	N
W/H	0.992	likely_pathogenic	0.9925	pathogenic	-2.408	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
W/I	0.9612	likely_pathogenic	0.9764	pathogenic	-2.334	Highly Destabilizing	0.995	D	0.846	deleterious	None	None	None	None	N
W/K	0.9994	likely_pathogenic	0.9995	pathogenic	-2.526	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
W/L	0.9213	likely_pathogenic	0.9459	pathogenic	-2.334	Highly Destabilizing	0.217	N	0.732	prob.delet.	D	0.710292917	None	None	N
W/M	0.9861	likely_pathogenic	0.9915	pathogenic	-1.702	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
W/N	0.9979	likely_pathogenic	0.9981	pathogenic	-3.227	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
W/P	0.9983	likely_pathogenic	0.9985	pathogenic	-2.666	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
W/Q	0.999	likely_pathogenic	0.9991	pathogenic	-3.071	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
W/R	0.9984	likely_pathogenic	0.9985	pathogenic	-2.23	Highly Destabilizing	0.999	D	0.865	deleterious	D	0.710494721	None	None	N
W/S	0.9881	likely_pathogenic	0.9902	pathogenic	-3.367	Highly Destabilizing	0.999	D	0.867	deleterious	D	0.710494721	None	None	N
W/T	0.9931	likely_pathogenic	0.9945	pathogenic	-3.182	Highly Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
W/V	0.9686	likely_pathogenic	0.9802	pathogenic	-2.666	Highly Destabilizing	0.995	D	0.838	deleterious	None	None	None	None	N
W/Y	0.8218	likely_pathogenic	0.8441	pathogenic	-1.894	Destabilizing	1.0	D	0.772	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.