TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23264	70015;70016;70017	chr2:178576342;178576341;178576340	chr2:179441069;179441068;179441067
N2AB	21623	65092;65093;65094	chr2:178576342;178576341;178576340	chr2:179441069;179441068;179441067
N2A	20696	62311;62312;62313	chr2:178576342;178576341;178576340	chr2:179441069;179441068;179441067
N2B	14199	42820;42821;42822	chr2:178576342;178576341;178576340	chr2:179441069;179441068;179441067
Novex-1	14324	43195;43196;43197	chr2:178576342;178576341;178576340	chr2:179441069;179441068;179441067
Novex-2	14391	43396;43397;43398	chr2:178576342;178576341;178576340	chr2:179441069;179441068;179441067
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-57
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1704
• 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
P/R	None	None	1.0	D	0.867	0.736	0.713262185059	gnomAD-4.0.0	2.12756E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.74611E-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
P/A	0.9098	likely_pathogenic	0.8984	pathogenic	-1.928	Destabilizing	1.0	D	0.8	deleterious	D	0.586936814	None	None	I
P/C	0.9899	likely_pathogenic	0.9882	pathogenic	-1.17	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
P/D	0.9988	likely_pathogenic	0.9986	pathogenic	-2.18	Highly Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
P/E	0.997	likely_pathogenic	0.9967	pathogenic	-2.129	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
P/F	0.9994	likely_pathogenic	0.9993	pathogenic	-1.43	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
P/G	0.9914	likely_pathogenic	0.9903	pathogenic	-2.316	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
P/H	0.9959	likely_pathogenic	0.9949	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.856	deleterious	D	0.635832474	None	None	I
P/I	0.9906	likely_pathogenic	0.9905	pathogenic	-0.912	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
P/K	0.9981	likely_pathogenic	0.9976	pathogenic	-1.719	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
P/L	0.9637	likely_pathogenic	0.9629	pathogenic	-0.912	Destabilizing	1.0	D	0.881	deleterious	D	0.618804092	None	None	I
P/M	0.9945	likely_pathogenic	0.9943	pathogenic	-0.566	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
P/N	0.9972	likely_pathogenic	0.9971	pathogenic	-1.505	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	I
P/Q	0.9946	likely_pathogenic	0.9939	pathogenic	-1.605	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/R	0.9939	likely_pathogenic	0.9921	pathogenic	-1.257	Destabilizing	1.0	D	0.867	deleterious	D	0.619611309	None	None	I
P/S	0.9817	likely_pathogenic	0.9784	pathogenic	-1.992	Destabilizing	1.0	D	0.819	deleterious	D	0.564245399	None	None	I
P/T	0.9714	likely_pathogenic	0.9686	pathogenic	-1.832	Destabilizing	1.0	D	0.813	deleterious	D	0.619409505	None	None	I
P/V	0.9725	likely_pathogenic	0.971	pathogenic	-1.22	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
P/W	0.9997	likely_pathogenic	0.9996	pathogenic	-1.763	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
P/Y	0.9993	likely_pathogenic	0.9991	pathogenic	-1.497	Destabilizing	1.0	D	0.879	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.