TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6118	18577;18578;18579	chr2:178729901;178729900;178729899	chr2:179594628;179594627;179594626
N2AB	5801	17626;17627;17628	chr2:178729901;178729900;178729899	chr2:179594628;179594627;179594626
N2A	4874	14845;14846;14847	chr2:178729901;178729900;178729899	chr2:179594628;179594627;179594626
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-45
• Domain position: 14
• Structural Position: 18
• Q(SASA): 0.7211
• 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
R/K	rs2154307652	None	0.003	N	0.352	0.1	0.279370189704	gnomAD-4.0.0	1.59235E-06	None	None	None	None	I	None	0	0	None	0	2.78087E-05	None	0	0	0	0	0
R/S	None	None	0.565	N	0.577	0.196	0.225215365344	gnomAD-4.0.0	3.18468E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.86632E-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
R/A	0.3937	ambiguous	0.3802	ambiguous	0.115	Stabilizing	0.633	D	0.567	neutral	None	None	None	None	I
R/C	0.2254	likely_benign	0.2299	benign	-0.103	Destabilizing	0.996	D	0.668	neutral	None	None	None	None	I
R/D	0.6505	likely_pathogenic	0.6357	pathogenic	-0.147	Destabilizing	0.923	D	0.567	neutral	None	None	None	None	I
R/E	0.3006	likely_benign	0.2926	benign	-0.081	Destabilizing	0.633	D	0.549	neutral	None	None	None	None	I
R/F	0.5887	likely_pathogenic	0.5914	pathogenic	-0.102	Destabilizing	0.987	D	0.623	neutral	None	None	None	None	I
R/G	0.2344	likely_benign	0.2185	benign	-0.072	Destabilizing	0.722	D	0.563	neutral	D	0.524824063	None	None	I
R/H	0.1262	likely_benign	0.1287	benign	-0.609	Destabilizing	0.961	D	0.508	neutral	None	None	None	None	I
R/I	0.3018	likely_benign	0.3113	benign	0.572	Stabilizing	0.961	D	0.625	neutral	None	None	None	None	I
R/K	0.1067	likely_benign	0.1045	benign	0.006	Stabilizing	0.003	N	0.352	neutral	N	0.405919379	None	None	I
R/L	0.2398	likely_benign	0.2343	benign	0.572	Stabilizing	0.775	D	0.563	neutral	None	None	None	None	I
R/M	0.2866	likely_benign	0.2868	benign	0.047	Stabilizing	0.995	D	0.532	neutral	N	0.500389765	None	None	I
R/N	0.5727	likely_pathogenic	0.564	pathogenic	0.145	Stabilizing	0.923	D	0.501	neutral	None	None	None	None	I
R/P	0.4317	ambiguous	0.4036	ambiguous	0.44	Stabilizing	0.961	D	0.605	neutral	None	None	None	None	I
R/Q	0.096	likely_benign	0.0955	benign	0.098	Stabilizing	0.858	D	0.519	neutral	None	None	None	None	I
R/S	0.4758	ambiguous	0.4592	ambiguous	-0.103	Destabilizing	0.565	D	0.577	neutral	N	0.475624607	None	None	I
R/T	0.2615	likely_benign	0.2573	benign	0.092	Stabilizing	0.722	D	0.53	neutral	N	0.464871682	None	None	I
R/V	0.3875	ambiguous	0.3938	ambiguous	0.44	Stabilizing	0.923	D	0.619	neutral	None	None	None	None	I
R/W	0.1616	likely_benign	0.1625	benign	-0.221	Destabilizing	0.995	D	0.673	neutral	D	0.533502261	None	None	I
R/Y	0.382	ambiguous	0.381	ambiguous	0.195	Stabilizing	0.987	D	0.609	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.