TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1736	5431;5432;5433	chr2:178776658;178776657;178776656	chr2:179641385;179641384;179641383
N2AB	1736	5431;5432;5433	chr2:178776658;178776657;178776656	chr2:179641385;179641384;179641383
N2A	1736	5431;5432;5433	chr2:178776658;178776657;178776656	chr2:179641385;179641384;179641383
N2B	1690	5293;5294;5295	chr2:178776658;178776657;178776656	chr2:179641385;179641384;179641383
Novex-1	1690	5293;5294;5295	chr2:178776658;178776657;178776656	chr2:179641385;179641384;179641383
Novex-2	1690	5293;5294;5295	chr2:178776658;178776657;178776656	chr2:179641385;179641384;179641383
Novex-3	1736	5431;5432;5433	chr2:178776658;178776657;178776656	chr2:179641385;179641384;179641383

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-8
• Domain position: 34
• Structural Position: 46
• Q(SASA): 0.2734
• 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
V/M	rs2092259333	None	1.0	D	0.76	0.759	0.758467727117	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/M	rs2092259333	None	1.0	D	0.76	0.759	0.758467727117	gnomAD-4.0.0	6.56875E-06	None	None	None	None	I	None	2.41208E-05	0	None	0	0	None	0	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
V/A	0.8857	likely_pathogenic	0.8723	pathogenic	-1.545	Destabilizing	0.999	D	0.667	neutral	D	0.752369831	None	None	I
V/C	0.9825	likely_pathogenic	0.9804	pathogenic	-0.85	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
V/D	0.9987	likely_pathogenic	0.9987	pathogenic	-1.481	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
V/E	0.994	likely_pathogenic	0.9936	pathogenic	-1.471	Destabilizing	1.0	D	0.866	deleterious	D	0.807966053	None	None	I
V/F	0.9421	likely_pathogenic	0.9398	pathogenic	-1.17	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
V/G	0.965	likely_pathogenic	0.9627	pathogenic	-1.882	Destabilizing	1.0	D	0.866	deleterious	D	0.807966053	None	None	I
V/H	0.9986	likely_pathogenic	0.9986	pathogenic	-1.502	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
V/I	0.1753	likely_benign	0.1615	benign	-0.706	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	I
V/K	0.9956	likely_pathogenic	0.9955	pathogenic	-1.338	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
V/L	0.8502	likely_pathogenic	0.8219	pathogenic	-0.706	Destabilizing	0.997	D	0.691	prob.neutral	D	0.636141943	None	None	I
V/M	0.8269	likely_pathogenic	0.8012	pathogenic	-0.449	Destabilizing	1.0	D	0.76	deleterious	D	0.736711137	None	None	I
V/N	0.9948	likely_pathogenic	0.9947	pathogenic	-1.034	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
V/P	0.991	likely_pathogenic	0.9908	pathogenic	-0.952	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
V/Q	0.9932	likely_pathogenic	0.9927	pathogenic	-1.186	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
V/R	0.9918	likely_pathogenic	0.9916	pathogenic	-0.832	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
V/S	0.971	likely_pathogenic	0.9689	pathogenic	-1.521	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
V/T	0.8283	likely_pathogenic	0.8138	pathogenic	-1.402	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
V/W	0.9988	likely_pathogenic	0.9987	pathogenic	-1.4	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
V/Y	0.9965	likely_pathogenic	0.9963	pathogenic	-1.126	Destabilizing	1.0	D	0.789	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.