TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8710	26353;26354;26355	chr2:178715058;178715057;178715056	chr2:179579785;179579784;179579783
N2AB	8393	25402;25403;25404	chr2:178715058;178715057;178715056	chr2:179579785;179579784;179579783
N2A	7466	22621;22622;22623	chr2:178715058;178715057;178715056	chr2:179579785;179579784;179579783
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-72
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2846
• 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
I/F	None	None	0.109	N	0.487	0.051	0.441844919209	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/L	rs530696557	-0.261	None	N	0.259	0.055	0.373173300195	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/L	rs530696557	-0.261	None	N	0.259	0.055	0.373173300195	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
I/M	None	None	0.001	N	0.281	0.081	0.188950314367	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
I/A	0.0949	likely_benign	0.1124	benign	-1.365	Destabilizing	0.001	N	0.145	neutral	None	None	None	None	N
I/C	0.5002	ambiguous	0.5782	pathogenic	-0.928	Destabilizing	0.452	N	0.521	neutral	None	None	None	None	N
I/D	0.4539	ambiguous	0.621	pathogenic	-0.443	Destabilizing	None	N	0.305	neutral	None	None	None	None	N
I/E	0.3318	likely_benign	0.4512	ambiguous	-0.443	Destabilizing	0.041	N	0.52	neutral	None	None	None	None	N
I/F	0.1222	likely_benign	0.1791	benign	-0.917	Destabilizing	0.109	N	0.487	neutral	N	0.476819472	None	None	N
I/G	0.3103	likely_benign	0.4294	ambiguous	-1.676	Destabilizing	0.055	N	0.483	neutral	None	None	None	None	N
I/H	0.3574	ambiguous	0.479	ambiguous	-0.809	Destabilizing	0.797	D	0.526	neutral	None	None	None	None	N
I/K	0.2207	likely_benign	0.3205	benign	-0.85	Destabilizing	0.003	N	0.536	neutral	None	None	None	None	N
I/L	0.0974	likely_benign	0.1226	benign	-0.601	Destabilizing	None	N	0.259	neutral	N	0.481859933	None	None	N
I/M	0.0768	likely_benign	0.0978	benign	-0.512	Destabilizing	0.001	N	0.281	neutral	N	0.482531936	None	None	N
I/N	0.1845	likely_benign	0.2538	benign	-0.701	Destabilizing	0.081	N	0.59	neutral	N	0.490402058	None	None	N
I/P	0.6057	likely_pathogenic	0.7462	pathogenic	-0.823	Destabilizing	0.452	N	0.589	neutral	None	None	None	None	N
I/Q	0.2639	likely_benign	0.3571	ambiguous	-0.834	Destabilizing	0.255	N	0.584	neutral	None	None	None	None	N
I/R	0.1466	likely_benign	0.2197	benign	-0.309	Destabilizing	0.139	N	0.59	neutral	None	None	None	None	N
I/S	0.1211	likely_benign	0.151	benign	-1.368	Destabilizing	0.018	N	0.449	neutral	N	0.412381205	None	None	N
I/T	0.0582	likely_benign	0.0631	benign	-1.24	Destabilizing	None	N	0.178	neutral	N	0.43196983	None	None	N
I/V	0.059	likely_benign	0.0609	benign	-0.823	Destabilizing	None	N	0.089	neutral	N	0.409959762	None	None	N
I/W	0.5977	likely_pathogenic	0.7448	pathogenic	-0.96	Destabilizing	0.934	D	0.561	neutral	None	None	None	None	N
I/Y	0.4108	ambiguous	0.5282	ambiguous	-0.729	Destabilizing	0.037	N	0.55	neutral	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.