TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32244	96955;96956;96957	chr2:178543243;178543242;178543241	chr2:179407970;179407969;179407968
N2AB	30603	92032;92033;92034	chr2:178543243;178543242;178543241	chr2:179407970;179407969;179407968
N2A	29676	89251;89252;89253	chr2:178543243;178543242;178543241	chr2:179407970;179407969;179407968
N2B	23179	69760;69761;69762	chr2:178543243;178543242;178543241	chr2:179407970;179407969;179407968
Novex-1	23304	70135;70136;70137	chr2:178543243;178543242;178543241	chr2:179407970;179407969;179407968
Novex-2	23371	70336;70337;70338	chr2:178543243;178543242;178543241	chr2:179407970;179407969;179407968
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-123
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.2461
• 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
A/V	None	None	0.061	N	0.207	0.151	0.200317383148	gnomAD-4.0.0	1.59117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85816E-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
A/C	0.5429	ambiguous	0.5193	ambiguous	-0.752	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	N
A/D	0.3512	ambiguous	0.3413	ambiguous	-0.654	Destabilizing	0.988	D	0.545	neutral	N	0.440231449	None	None	N
A/E	0.2446	likely_benign	0.2485	benign	-0.737	Destabilizing	0.991	D	0.474	neutral	None	None	None	None	N
A/F	0.3161	likely_benign	0.2884	benign	-0.996	Destabilizing	0.982	D	0.567	neutral	None	None	None	None	N
A/G	0.1669	likely_benign	0.1567	benign	-0.914	Destabilizing	0.959	D	0.471	neutral	N	0.436692498	None	None	N
A/H	0.4683	ambiguous	0.4541	ambiguous	-1.012	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	N
A/I	0.2009	likely_benign	0.1789	benign	-0.376	Destabilizing	0.884	D	0.449	neutral	None	None	None	None	N
A/K	0.4293	ambiguous	0.4243	ambiguous	-0.976	Destabilizing	0.982	D	0.451	neutral	None	None	None	None	N
A/L	0.1751	likely_benign	0.1619	benign	-0.376	Destabilizing	0.046	N	0.288	neutral	None	None	None	None	N
A/M	0.1988	likely_benign	0.1811	benign	-0.295	Destabilizing	0.982	D	0.517	neutral	None	None	None	None	N
A/N	0.2737	likely_benign	0.2527	benign	-0.599	Destabilizing	0.991	D	0.564	neutral	None	None	None	None	N
A/P	0.297	likely_benign	0.263	benign	-0.451	Destabilizing	0.996	D	0.507	neutral	N	0.440290164	None	None	N
A/Q	0.3174	likely_benign	0.3213	benign	-0.806	Destabilizing	0.997	D	0.528	neutral	None	None	None	None	N
A/R	0.4072	ambiguous	0.4216	ambiguous	-0.582	Destabilizing	0.991	D	0.52	neutral	None	None	None	None	N
A/S	0.1075	likely_benign	0.1046	benign	-0.938	Destabilizing	0.852	D	0.483	neutral	N	0.4190481	None	None	N
A/T	0.1008	likely_benign	0.0928	benign	-0.927	Destabilizing	0.134	N	0.336	neutral	N	0.440788809	None	None	N
A/V	0.0991	likely_benign	0.0926	benign	-0.451	Destabilizing	0.061	N	0.207	neutral	N	0.418354667	None	None	N
A/W	0.6689	likely_pathogenic	0.6533	pathogenic	-1.243	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
A/Y	0.4161	ambiguous	0.3913	ambiguous	-0.867	Destabilizing	0.997	D	0.574	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.