TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25616	77071;77072;77073	chr2:178569286;178569285;178569284	chr2:179434013;179434012;179434011
N2AB	23975	72148;72149;72150	chr2:178569286;178569285;178569284	chr2:179434013;179434012;179434011
N2A	23048	69367;69368;69369	chr2:178569286;178569285;178569284	chr2:179434013;179434012;179434011
N2B	16551	49876;49877;49878	chr2:178569286;178569285;178569284	chr2:179434013;179434012;179434011
Novex-1	16676	50251;50252;50253	chr2:178569286;178569285;178569284	chr2:179434013;179434012;179434011
Novex-2	16743	50452;50453;50454	chr2:178569286;178569285;178569284	chr2:179434013;179434012;179434011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-74
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.5265
• 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
D/N	None	None	0.006	N	0.133	0.077	0.151104730317	gnomAD-4.0.0	1.59988E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87379E-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
D/A	0.1702	likely_benign	0.2033	benign	-0.46	Destabilizing	0.822	D	0.488	neutral	N	0.487462031	None	None	N
D/C	0.5604	ambiguous	0.612	pathogenic	-0.037	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
D/E	0.1152	likely_benign	0.1332	benign	-0.769	Destabilizing	0.656	D	0.465	neutral	N	0.464705819	None	None	N
D/F	0.5195	ambiguous	0.5679	pathogenic	-0.643	Destabilizing	0.993	D	0.637	neutral	None	None	None	None	N
D/G	0.1503	likely_benign	0.1669	benign	-0.719	Destabilizing	0.698	D	0.433	neutral	N	0.504474928	None	None	N
D/H	0.2883	likely_benign	0.3221	benign	-0.95	Destabilizing	0.97	D	0.515	neutral	N	0.477422399	None	None	N
D/I	0.4152	ambiguous	0.4747	ambiguous	0.192	Stabilizing	0.978	D	0.621	neutral	None	None	None	None	N
D/K	0.4137	ambiguous	0.4648	ambiguous	-0.118	Destabilizing	0.86	D	0.489	neutral	None	None	None	None	N
D/L	0.3752	ambiguous	0.4326	ambiguous	0.192	Stabilizing	0.978	D	0.615	neutral	None	None	None	None	N
D/M	0.513	ambiguous	0.5787	pathogenic	0.658	Stabilizing	0.998	D	0.631	neutral	None	None	None	None	N
D/N	0.0787	likely_benign	0.0898	benign	-0.375	Destabilizing	0.006	N	0.133	neutral	N	0.464241672	None	None	N
D/P	0.9361	likely_pathogenic	0.9443	pathogenic	-0.002	Destabilizing	0.993	D	0.503	neutral	None	None	None	None	N
D/Q	0.2969	likely_benign	0.3456	ambiguous	-0.344	Destabilizing	0.956	D	0.49	neutral	None	None	None	None	N
D/R	0.499	ambiguous	0.5443	ambiguous	-0.147	Destabilizing	0.956	D	0.569	neutral	None	None	None	None	N
D/S	0.1062	likely_benign	0.1275	benign	-0.562	Destabilizing	0.754	D	0.424	neutral	None	None	None	None	N
D/T	0.1518	likely_benign	0.188	benign	-0.357	Destabilizing	0.86	D	0.485	neutral	None	None	None	None	N
D/V	0.2539	likely_benign	0.2956	benign	-0.002	Destabilizing	0.97	D	0.617	neutral	N	0.517176081	None	None	N
D/W	0.8745	likely_pathogenic	0.8917	pathogenic	-0.604	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
D/Y	0.2235	likely_benign	0.2416	benign	-0.426	Destabilizing	0.99	D	0.637	neutral	N	0.516922592	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.