TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21211	63856;63857;63858	chr2:178587678;178587677;178587676	chr2:179452405;179452404;179452403
N2AB	19570	58933;58934;58935	chr2:178587678;178587677;178587676	chr2:179452405;179452404;179452403
N2A	18643	56152;56153;56154	chr2:178587678;178587677;178587676	chr2:179452405;179452404;179452403
N2B	12146	36661;36662;36663	chr2:178587678;178587677;178587676	chr2:179452405;179452404;179452403
Novex-1	12271	37036;37037;37038	chr2:178587678;178587677;178587676	chr2:179452405;179452404;179452403
Novex-2	12338	37237;37238;37239	chr2:178587678;178587677;178587676	chr2:179452405;179452404;179452403
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-123
• Domain position: 35
• Structural Position: 51
• Q(SASA): 0.6412
• 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/A	rs397517654	None	0.565	N	0.434	0.225	0.367042808489	gnomAD-4.0.0	2.05364E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69916E-06	0	0
V/I	None	None	0.034	N	0.347	0.036	0.26169431596	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.1293	likely_benign	0.1255	benign	-0.754	Destabilizing	0.565	D	0.434	neutral	N	0.385327024	None	None	I
V/C	0.6819	likely_pathogenic	0.6834	pathogenic	-0.853	Destabilizing	0.996	D	0.497	neutral	None	None	None	None	I
V/D	0.3066	likely_benign	0.2472	benign	-0.31	Destabilizing	0.983	D	0.622	neutral	N	0.31315192	None	None	I
V/E	0.2539	likely_benign	0.2093	benign	-0.355	Destabilizing	0.961	D	0.565	neutral	None	None	None	None	I
V/F	0.2031	likely_benign	0.1889	benign	-0.598	Destabilizing	0.901	D	0.464	neutral	N	0.488819538	None	None	I
V/G	0.1971	likely_benign	0.1857	benign	-0.974	Destabilizing	0.949	D	0.609	neutral	N	0.401216409	None	None	I
V/H	0.5503	ambiguous	0.5266	ambiguous	-0.362	Destabilizing	0.996	D	0.626	neutral	None	None	None	None	I
V/I	0.0899	likely_benign	0.0936	benign	-0.292	Destabilizing	0.034	N	0.347	neutral	N	0.478045184	None	None	I
V/K	0.4308	ambiguous	0.3737	ambiguous	-0.727	Destabilizing	0.923	D	0.563	neutral	None	None	None	None	I
V/L	0.1932	likely_benign	0.183	benign	-0.292	Destabilizing	0.156	N	0.391	neutral	N	0.406761088	None	None	I
V/M	0.1271	likely_benign	0.1238	benign	-0.482	Destabilizing	0.096	N	0.283	neutral	None	None	None	None	I
V/N	0.2252	likely_benign	0.2099	benign	-0.597	Destabilizing	0.961	D	0.632	neutral	None	None	None	None	I
V/P	0.3376	likely_benign	0.3359	benign	-0.41	Destabilizing	0.987	D	0.565	neutral	None	None	None	None	I
V/Q	0.3261	likely_benign	0.2936	benign	-0.74	Destabilizing	0.961	D	0.578	neutral	None	None	None	None	I
V/R	0.4284	ambiguous	0.3588	ambiguous	-0.241	Destabilizing	0.923	D	0.632	neutral	None	None	None	None	I
V/S	0.1793	likely_benign	0.1732	benign	-1.06	Destabilizing	0.923	D	0.495	neutral	None	None	None	None	I
V/T	0.1244	likely_benign	0.1244	benign	-0.991	Destabilizing	0.775	D	0.397	neutral	None	None	None	None	I
V/W	0.7574	likely_pathogenic	0.732	pathogenic	-0.715	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	I
V/Y	0.4926	ambiguous	0.48	ambiguous	-0.426	Destabilizing	0.961	D	0.466	neutral	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.