TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29011	87256;87257;87258	chr2:178558428;178558427;178558426	chr2:179423155;179423154;179423153
N2AB	27370	82333;82334;82335	chr2:178558428;178558427;178558426	chr2:179423155;179423154;179423153
N2A	26443	79552;79553;79554	chr2:178558428;178558427;178558426	chr2:179423155;179423154;179423153
N2B	19946	60061;60062;60063	chr2:178558428;178558427;178558426	chr2:179423155;179423154;179423153
Novex-1	20071	60436;60437;60438	chr2:178558428;178558427;178558426	chr2:179423155;179423154;179423153
Novex-2	20138	60637;60638;60639	chr2:178558428;178558427;178558426	chr2:179423155;179423154;179423153
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: Fn3-99
• Domain position: 70
• Structural Position: 104
• Q(SASA): 0.107
• 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/H	rs2154156569	None	1.0	D	0.857	0.875	0.778320552042	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
Y/A	0.968	likely_pathogenic	0.9603	pathogenic	-2.737	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/C	0.7275	likely_pathogenic	0.6933	pathogenic	-1.356	Destabilizing	1.0	D	0.897	deleterious	D	0.678043517	None	None	N
Y/D	0.9844	likely_pathogenic	0.9786	pathogenic	-3.167	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.678043517	None	None	N
Y/E	0.9941	likely_pathogenic	0.9931	pathogenic	-2.945	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
Y/F	0.1887	likely_benign	0.1944	benign	-0.877	Destabilizing	0.999	D	0.763	deleterious	D	0.616560963	None	None	N
Y/G	0.96	likely_pathogenic	0.9436	pathogenic	-3.163	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
Y/H	0.9024	likely_pathogenic	0.9041	pathogenic	-1.887	Destabilizing	1.0	D	0.857	deleterious	D	0.661791991	None	None	N
Y/I	0.7896	likely_pathogenic	0.806	pathogenic	-1.323	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
Y/K	0.9912	likely_pathogenic	0.9909	pathogenic	-1.927	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
Y/L	0.778	likely_pathogenic	0.7965	pathogenic	-1.323	Destabilizing	0.997	D	0.832	deleterious	None	None	None	None	N
Y/M	0.8891	likely_pathogenic	0.8816	pathogenic	-1.033	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/N	0.8773	likely_pathogenic	0.8522	pathogenic	-2.777	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.677841713	None	None	N
Y/P	0.9985	likely_pathogenic	0.9982	pathogenic	-1.809	Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
Y/Q	0.9869	likely_pathogenic	0.9859	pathogenic	-2.477	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
Y/R	0.9786	likely_pathogenic	0.9794	pathogenic	-1.836	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/S	0.942	likely_pathogenic	0.923	pathogenic	-3.1	Highly Destabilizing	1.0	D	0.915	deleterious	D	0.678043517	None	None	N
Y/T	0.962	likely_pathogenic	0.954	pathogenic	-2.752	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
Y/V	0.713	likely_pathogenic	0.7181	pathogenic	-1.809	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/W	0.8453	likely_pathogenic	0.8502	pathogenic	-0.199	Destabilizing	1.0	D	0.837	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.