TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13742	41449;41450;41451	chr2:178636503;178636502;178636501	chr2:179501230;179501229;179501228
N2AB	12101	36526;36527;36528	chr2:178636503;178636502;178636501	chr2:179501230;179501229;179501228
N2A	11174	33745;33746;33747	chr2:178636503;178636502;178636501	chr2:179501230;179501229;179501228
N2B	4677	14254;14255;14256	chr2:178636503;178636502;178636501	chr2:179501230;179501229;179501228
Novex-1	4802	14629;14630;14631	chr2:178636503;178636502;178636501	chr2:179501230;179501229;179501228
Novex-2	4869	14830;14831;14832	chr2:178636503;178636502;178636501	chr2:179501230;179501229;179501228
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-87
• Domain position: 59
• Structural Position: 137
• Q(SASA): 0.1492
• 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
K/E	None	None	0.999	N	0.583	0.403	0.433713641954	gnomAD-4.0.0	1.59195E-06	None	None	None	None	N	None	0	2.28686E-05	None	0	0	None	0	0	0	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
K/A	0.9683	likely_pathogenic	0.97	pathogenic	-0.982	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
K/C	0.9792	likely_pathogenic	0.9777	pathogenic	-1.088	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
K/D	0.9969	likely_pathogenic	0.9965	pathogenic	-1.26	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/E	0.9735	likely_pathogenic	0.9646	pathogenic	-1.034	Destabilizing	0.999	D	0.583	neutral	N	0.50744401	None	None	N
K/F	0.992	likely_pathogenic	0.9927	pathogenic	-0.192	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
K/G	0.9862	likely_pathogenic	0.9865	pathogenic	-1.455	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/H	0.8699	likely_pathogenic	0.8553	pathogenic	-1.719	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/I	0.9392	likely_pathogenic	0.9209	pathogenic	0.319	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
K/L	0.934	likely_pathogenic	0.9315	pathogenic	0.319	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/M	0.8387	likely_pathogenic	0.8264	pathogenic	0.069	Stabilizing	1.0	D	0.747	deleterious	N	0.513991678	None	None	N
K/N	0.9876	likely_pathogenic	0.9845	pathogenic	-1.458	Destabilizing	1.0	D	0.679	prob.neutral	N	0.50770616	None	None	N
K/P	0.9992	likely_pathogenic	0.9992	pathogenic	-0.088	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/Q	0.7375	likely_pathogenic	0.699	pathogenic	-1.238	Destabilizing	1.0	D	0.663	neutral	N	0.510265694	None	None	N
K/R	0.2727	likely_benign	0.238	benign	-1.221	Destabilizing	0.999	D	0.587	neutral	N	0.491505003	None	None	N
K/S	0.9797	likely_pathogenic	0.9776	pathogenic	-1.978	Destabilizing	0.999	D	0.598	neutral	None	None	None	None	N
K/T	0.8955	likely_pathogenic	0.8658	pathogenic	-1.514	Destabilizing	1.0	D	0.721	prob.delet.	N	0.472374103	None	None	N
K/V	0.9162	likely_pathogenic	0.8999	pathogenic	-0.088	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/W	0.9915	likely_pathogenic	0.9908	pathogenic	-0.236	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/Y	0.9684	likely_pathogenic	0.9686	pathogenic	0.084	Stabilizing	1.0	D	0.791	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.