TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19070	57433;57434;57435	chr2:178597962;178597961;178597960	chr2:179462689;179462688;179462687
N2AB	17429	52510;52511;52512	chr2:178597962;178597961;178597960	chr2:179462689;179462688;179462687
N2A	16502	49729;49730;49731	chr2:178597962;178597961;178597960	chr2:179462689;179462688;179462687
N2B	10005	30238;30239;30240	chr2:178597962;178597961;178597960	chr2:179462689;179462688;179462687
Novex-1	10130	30613;30614;30615	chr2:178597962;178597961;178597960	chr2:179462689;179462688;179462687
Novex-2	10197	30814;30815;30816	chr2:178597962;178597961;178597960	chr2:179462689;179462688;179462687
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-26
• Domain position: 83
• Structural Position: 115
• Q(SASA): 0.1772
• 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/C	rs754134244	-0.769	1.0	D	0.832	0.573	0.857617907083	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
G/C	rs754134244	-0.769	1.0	D	0.832	0.573	0.857617907083	gnomAD-4.0.0	1.59226E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43336E-05	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	0.827	likely_pathogenic	0.7574	pathogenic	-0.705	Destabilizing	0.604	D	0.533	neutral	D	0.539254625	None	None	I
G/C	0.9258	likely_pathogenic	0.8579	pathogenic	-1.041	Destabilizing	1.0	D	0.832	deleterious	D	0.558626328	None	None	I
G/D	0.9268	likely_pathogenic	0.8896	pathogenic	-1.039	Destabilizing	0.999	D	0.895	deleterious	D	0.535242154	None	None	I
G/E	0.961	likely_pathogenic	0.9335	pathogenic	-1.174	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	I
G/F	0.9932	likely_pathogenic	0.9884	pathogenic	-1.212	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
G/H	0.9832	likely_pathogenic	0.9693	pathogenic	-0.972	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
G/I	0.9902	likely_pathogenic	0.9821	pathogenic	-0.665	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
G/K	0.9798	likely_pathogenic	0.9636	pathogenic	-1.251	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	I
G/L	0.9856	likely_pathogenic	0.9778	pathogenic	-0.665	Destabilizing	0.998	D	0.88	deleterious	None	None	None	None	I
G/M	0.9901	likely_pathogenic	0.9839	pathogenic	-0.569	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
G/N	0.9509	likely_pathogenic	0.9242	pathogenic	-0.904	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	I
G/P	0.9987	likely_pathogenic	0.9978	pathogenic	-0.642	Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	I
G/Q	0.9652	likely_pathogenic	0.9397	pathogenic	-1.204	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
G/R	0.9508	likely_pathogenic	0.9129	pathogenic	-0.738	Destabilizing	0.999	D	0.887	deleterious	D	0.539761604	None	None	I
G/S	0.6891	likely_pathogenic	0.5897	pathogenic	-1.081	Destabilizing	0.997	D	0.811	deleterious	D	0.539001136	None	None	I
G/T	0.9435	likely_pathogenic	0.904	pathogenic	-1.152	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	I
G/V	0.9752	likely_pathogenic	0.953	pathogenic	-0.642	Destabilizing	0.997	D	0.88	deleterious	D	0.539254625	None	None	I
G/W	0.9866	likely_pathogenic	0.9745	pathogenic	-1.379	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/Y	0.9873	likely_pathogenic	0.9754	pathogenic	-1.06	Destabilizing	1.0	D	0.881	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.