TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8819	26680;26681;26682	chr2:178714319;178714318;178714317	chr2:179579046;179579045;179579044
N2AB	8502	25729;25730;25731	chr2:178714319;178714318;178714317	chr2:179579046;179579045;179579044
N2A	7575	22948;22949;22950	chr2:178714319;178714318;178714317	chr2:179579046;179579045;179579044
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-73
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.2231
• 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
E/D	rs1242327696	-1.243	0.942	N	0.447	0.358	0.358540694251	gnomAD-2.1.1	1.91058E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.88752E-04	0
E/D	rs1242327696	-1.243	0.942	N	0.447	0.358	0.358540694251	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.02926E-04	0	0
E/D	rs1242327696	-1.243	0.942	N	0.447	0.358	0.358540694251	gnomAD-4.0.0	4.60109E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.02926E-04	0	0
E/K	rs1452521377	None	0.996	N	0.445	0.412	0.508223314113	gnomAD-4.0.0	2.73754E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5989E-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
E/A	0.1996	likely_benign	0.2135	benign	-0.822	Destabilizing	0.984	D	0.515	neutral	N	0.509107091	None	None	N
E/C	0.93	likely_pathogenic	0.9475	pathogenic	-0.553	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/D	0.2165	likely_benign	0.2318	benign	-1.202	Destabilizing	0.942	D	0.447	neutral	N	0.509614071	None	None	N
E/F	0.8366	likely_pathogenic	0.8492	pathogenic	-0.017	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/G	0.2514	likely_benign	0.2798	benign	-1.228	Destabilizing	0.999	D	0.671	neutral	D	0.536872585	None	None	N
E/H	0.6272	likely_pathogenic	0.6577	pathogenic	-0.297	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
E/I	0.4596	ambiguous	0.5019	ambiguous	0.304	Stabilizing	0.996	D	0.767	deleterious	None	None	None	None	N
E/K	0.2636	likely_benign	0.2887	benign	-0.911	Destabilizing	0.996	D	0.445	neutral	N	0.493267334	None	None	N
E/L	0.531	ambiguous	0.5833	pathogenic	0.304	Stabilizing	0.996	D	0.685	prob.neutral	None	None	None	None	N
E/M	0.5406	ambiguous	0.5817	pathogenic	0.756	Stabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
E/N	0.3907	ambiguous	0.4083	ambiguous	-1.401	Destabilizing	0.996	D	0.579	neutral	None	None	None	None	N
E/P	0.8925	likely_pathogenic	0.9148	pathogenic	-0.051	Destabilizing	0.996	D	0.75	deleterious	None	None	None	None	N
E/Q	0.1842	likely_benign	0.1978	benign	-1.207	Destabilizing	0.999	D	0.591	neutral	D	0.53687064	None	None	N
E/R	0.4431	ambiguous	0.4802	ambiguous	-0.528	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
E/S	0.2664	likely_benign	0.2762	benign	-1.765	Destabilizing	0.976	D	0.436	neutral	None	None	None	None	N
E/T	0.2554	likely_benign	0.273	benign	-1.427	Destabilizing	0.606	D	0.385	neutral	None	None	None	None	N
E/V	0.253	likely_benign	0.289	benign	-0.051	Destabilizing	0.993	D	0.669	neutral	N	0.48930777	None	None	N
E/W	0.9445	likely_pathogenic	0.9502	pathogenic	0.239	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/Y	0.7253	likely_pathogenic	0.7519	pathogenic	0.218	Stabilizing	1.0	D	0.773	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.