TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35175	105748;105749;105750	chr2:178531092;178531091;178531090	chr2:179395819;179395818;179395817
N2AB	33534	100825;100826;100827	chr2:178531092;178531091;178531090	chr2:179395819;179395818;179395817
N2A	32607	98044;98045;98046	chr2:178531092;178531091;178531090	chr2:179395819;179395818;179395817
N2B	26110	78553;78554;78555	chr2:178531092;178531091;178531090	chr2:179395819;179395818;179395817
Novex-1	26235	78928;78929;78930	chr2:178531092;178531091;178531090	chr2:179395819;179395818;179395817
Novex-2	26302	79129;79130;79131	chr2:178531092;178531091;178531090	chr2:179395819;179395818;179395817
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-164
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.0749
• 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
H/Q	rs1215297501	None	0.938	N	0.587	0.225	0.241078983079	gnomAD-4.0.0	3.18173E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71497E-06	0	0
H/Y	None	None	0.001	N	0.156	0.099	0.188950314367	gnomAD-4.0.0	1.59087E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02334E-05

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
H/A	0.6415	likely_pathogenic	0.6004	pathogenic	-1.55	Destabilizing	0.276	N	0.493	neutral	None	None	None	None	N
H/C	0.2554	likely_benign	0.2156	benign	-1.093	Destabilizing	0.987	D	0.649	neutral	None	None	None	None	N
H/D	0.5813	likely_pathogenic	0.5733	pathogenic	-0.938	Destabilizing	0.812	D	0.616	neutral	D	0.527960369	None	None	N
H/E	0.5041	ambiguous	0.4963	ambiguous	-0.787	Destabilizing	0.652	D	0.467	neutral	None	None	None	None	N
H/F	0.3607	ambiguous	0.3265	benign	-0.246	Destabilizing	0.003	N	0.341	neutral	None	None	None	None	N
H/G	0.6581	likely_pathogenic	0.5934	pathogenic	-1.95	Destabilizing	0.652	D	0.582	neutral	None	None	None	None	N
H/I	0.5115	ambiguous	0.4578	ambiguous	-0.403	Destabilizing	0.005	N	0.455	neutral	None	None	None	None	N
H/K	0.4965	ambiguous	0.4657	ambiguous	-1.141	Destabilizing	0.652	D	0.57	neutral	None	None	None	None	N
H/L	0.196	likely_benign	0.1724	benign	-0.403	Destabilizing	0.059	N	0.504	neutral	N	0.456230769	None	None	N
H/M	0.6607	likely_pathogenic	0.6214	pathogenic	-0.685	Destabilizing	0.868	D	0.659	neutral	None	None	None	None	N
H/N	0.2436	likely_benign	0.2283	benign	-1.442	Destabilizing	0.586	D	0.518	neutral	D	0.535598417	None	None	N
H/P	0.7105	likely_pathogenic	0.6875	pathogenic	-0.77	Destabilizing	0.938	D	0.686	prob.neutral	D	0.535771775	None	None	N
H/Q	0.2838	likely_benign	0.2748	benign	-1.134	Destabilizing	0.938	D	0.587	neutral	N	0.512702915	None	None	N
H/R	0.2095	likely_benign	0.1881	benign	-1.315	Destabilizing	0.586	D	0.549	neutral	N	0.478320982	None	None	N
H/S	0.4694	ambiguous	0.4392	ambiguous	-1.736	Destabilizing	0.652	D	0.552	neutral	None	None	None	None	N
H/T	0.5635	ambiguous	0.4979	ambiguous	-1.462	Destabilizing	0.481	N	0.585	neutral	None	None	None	None	N
H/V	0.4697	ambiguous	0.4106	ambiguous	-0.77	Destabilizing	0.002	N	0.424	neutral	None	None	None	None	N
H/W	0.4101	ambiguous	0.3709	ambiguous	0.245	Stabilizing	0.961	D	0.625	neutral	None	None	None	None	N
H/Y	0.1024	likely_benign	0.0867	benign	0.275	Stabilizing	0.001	N	0.156	neutral	N	0.43793301	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.