TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30149	90670;90671;90672	chr2:178552455;178552454;178552453	chr2:179417182;179417181;179417180
N2AB	28508	85747;85748;85749	chr2:178552455;178552454;178552453	chr2:179417182;179417181;179417180
N2A	27581	82966;82967;82968	chr2:178552455;178552454;178552453	chr2:179417182;179417181;179417180
N2B	21084	63475;63476;63477	chr2:178552455;178552454;178552453	chr2:179417182;179417181;179417180
Novex-1	21209	63850;63851;63852	chr2:178552455;178552454;178552453	chr2:179417182;179417181;179417180
Novex-2	21276	64051;64052;64053	chr2:178552455;178552454;178552453	chr2:179417182;179417181;179417180
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-148
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2205
• 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
V/M	rs1699816128	None	0.901	N	0.665	0.262	0.388010793773	gnomAD-4.0.0	1.60543E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.04822E-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
V/A	0.4739	ambiguous	0.4561	ambiguous	-1.622	Destabilizing	0.517	D	0.585	neutral	N	0.452920239	None	None	N
V/C	0.7819	likely_pathogenic	0.7667	pathogenic	-1.188	Destabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	N
V/D	0.9612	likely_pathogenic	0.9615	pathogenic	-1.317	Destabilizing	0.987	D	0.792	deleterious	None	None	None	None	N
V/E	0.9262	likely_pathogenic	0.9316	pathogenic	-1.236	Destabilizing	0.983	D	0.745	deleterious	N	0.499821251	None	None	N
V/F	0.2745	likely_benign	0.3114	benign	-1.067	Destabilizing	0.923	D	0.755	deleterious	None	None	None	None	N
V/G	0.6777	likely_pathogenic	0.6646	pathogenic	-2.036	Highly Destabilizing	0.949	D	0.765	deleterious	N	0.499821251	None	None	N
V/H	0.9553	likely_pathogenic	0.9613	pathogenic	-1.549	Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	N
V/I	0.0721	likely_benign	0.078	benign	-0.549	Destabilizing	0.005	N	0.227	neutral	None	None	None	None	N
V/K	0.9421	likely_pathogenic	0.9486	pathogenic	-1.357	Destabilizing	0.961	D	0.739	prob.delet.	None	None	None	None	N
V/L	0.1663	likely_benign	0.2284	benign	-0.549	Destabilizing	0.003	N	0.202	neutral	N	0.450765369	None	None	N
V/M	0.2056	likely_benign	0.2302	benign	-0.478	Destabilizing	0.901	D	0.665	neutral	N	0.488211456	None	None	N
V/N	0.8956	likely_pathogenic	0.9002	pathogenic	-1.295	Destabilizing	0.987	D	0.795	deleterious	None	None	None	None	N
V/P	0.9735	likely_pathogenic	0.9756	pathogenic	-0.872	Destabilizing	0.987	D	0.755	deleterious	None	None	None	None	N
V/Q	0.9043	likely_pathogenic	0.9085	pathogenic	-1.323	Destabilizing	0.987	D	0.756	deleterious	None	None	None	None	N
V/R	0.9142	likely_pathogenic	0.9162	pathogenic	-0.968	Destabilizing	0.961	D	0.795	deleterious	None	None	None	None	N
V/S	0.7594	likely_pathogenic	0.7358	pathogenic	-1.936	Destabilizing	0.961	D	0.741	deleterious	None	None	None	None	N
V/T	0.5545	ambiguous	0.5555	ambiguous	-1.717	Destabilizing	0.775	D	0.62	neutral	None	None	None	None	N
V/W	0.9438	likely_pathogenic	0.9565	pathogenic	-1.336	Destabilizing	0.996	D	0.761	deleterious	None	None	None	None	N
V/Y	0.8256	likely_pathogenic	0.8391	pathogenic	-1.01	Destabilizing	0.961	D	0.768	deleterious	None	None	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.